Cyclophosphamide: Review of its mutagenicity for an assessment of potential germ cell risks

Abe, 1983, Induction by indirect mutagens/carcinogens, aryl hydrocarbon hydroxylase activity and benzo[a]pyrene metabolism in cultured human hepatoma cells, Mutation Res., 109, 83, 10.1016/0027-5107(83)90097-0 Abe, 1981, Activation of cyclophosphamide using perfused rat liver system and induction of sister chromatid exchanges in vitro, Hum Genet., 58, 349, 10.1007/BF00294936 Adler, 1983, ICPEM Working Paper 4/3: Comparison of types of chemically induced genetic changes in mammals, Mutation Res., 115, 293, 10.1016/0165-1110(83)90008-8 Albanese, 1987, Mammalian male germ cell cytogenetics, Mutagenesis, 2, 79, 10.1093/mutage/2.2.79 Albanese, 1987, Induction and transmission of chemically induced chromosome aberrations in female germ cells, Environ. Mol. Mutagen., 10, 231, 10.1002/em.2850100303 Albertini, 1991, Reevaluation of the 9 compounds reported conclusive positive in yeast Saccharomyces cerevisiae aneuploidy test systems by the Gene-Tox program using strain D61.M of Saccharomyces cerevisiae, Mutation Res., 260, 165, 10.1016/0165-1218(91)90005-7 Alivizitos, 1991, Bladder cancer in a young girl with systemic lupus erythematous treated with cyclophosphamide, Acta Urol. Belg., 59, 133 Allen, 1976, In vivo BrdU-33258 Hoechst analysis of DNA replication kinetics and sister chromatid exchange formation in mouse somatic and meiotic cells, Chromosoma, 58, 325, 10.1007/BF00292841 Allen, 1987, Synaptonemal complex damage as a measure of chemical mutagen effects on mammalian germ cells, Mutation Res., 190, 19, 10.1016/0165-7992(87)90076-5 Allen, 1988, Synaptonemal complex damage as a measure of genotoxicity at meiosis, Cell Biol. Toxicol., 4, 487, 10.1007/BF00117776 Ammenheuser, 1988, Elevated frequencies of 6-thioguanine-resistant lymphocytes in multiple sclerosis patients treated with cyclophosphamide: a prospective study, Mutation Res., 204, 509, 10.1016/0165-1218(88)90045-6 Anderson, 1976, Vinyl chloride: dominant lethal studies in male CD-1 mice, Mutation Res., 40, 359, 10.1016/0165-1218(76)90034-3 Appelgren, 1978, Testing of ethylene oxide for mutagenicity using the micronucleus test in mice and rats, Acta Pharmacol. Toxicol., 43, 69, 10.1111/j.1600-0773.1978.tb02235.x Arrighi, 1962, Chromosome damage in murine and human cells following cytoxan therapy, Tex. Rep. Biol. Med., 20, 545 Ataya, 1990, The uptake and metabolism of cyclophosphamide by the ovary, Select. Cancer Ther., 6, 83, 10.1089/sct.1990.6.83 Au, 1980, Short-term cytogenetic assays of nine cancer chemotherapeutic drugs with metabolic activation, Environ. Mutagen., 2, 455, 10.1002/em.2860020404 Auroux, 1990, Cyclophosphamide in the F0 male rat: physical and behavorial changes in three successive adult generations, Mutation Res., 229, 189, 10.1016/0027-5107(90)90093-J Backer, 1988, Synaptonemal complex damage in relation to meiotic chromosome aberrations after exposure of male mice to cyclophosphamide, Mutation Res., 203, 317, 10.1016/0165-1161(88)90021-0 Bagley, 1973, Clinical pharmacology of cyclophosphamide, Cancer Res., 33, 226 Barbarasa, 1979, In vivo cytogenetic screening for determination of the mutagenic potential of cyclophosphamide, Rev. Roum. Morphol. Embryol. Physiol., 25, 369 Batiste-Alentorn, 1991, Genotoxicity studies with the unstable zeste-white (UZ) system of Drosophila melanogaster: results with ten carcinogenic compounds, Environ. Mol. Mutagen., 18, 120, 10.1002/em.2850180207 Becker, 1982, Expression of genetic damage induced by alkylating agents in germ cells of female mice, Mutation Res., 92, 447, 10.1016/0027-5107(82)90243-3 Benning, 1992, Detection of micronuclei after exposure to mitomycin C, cyclophosphamide and diethylnitrosamine by the in vivo micronucleus test in mouse splenocytes, Mutation Res., 280, 137, 10.1016/0165-1218(92)90009-O BEIR, 1980, Genetic effects, 71 BEIR, 1990, Genetic effects of radiation, 65 Benedict, 1978, Cyclophosphamide-induced oncogenic transformation, chromosomal breakage, and sister chromatid exchange following microsomal activation, Cancer Res., 38, 2922 Benson, 1988, N-(2-major hydroxyethyl)-N-[2-(7-guaninyl)ethyl]amine, the putative DNA adduct of cyclophosphamide in vitro and in vivo in the rat, Biochem. Pharmacol., 37, 2979, 10.1016/0006-2952(88)90285-7 Bentley, 1988, Activity of germ-cell mutagens and nonmutagens in the rat spermatocyte UDS assay, Mutation Res., 203, 135, 10.1016/0165-1161(88)90028-3 Bigbee, 1990, The effect of chemotherapy on the in vivo frequency of glycophorin A ‘null’ variant erythrocytes, Mutation Res., 240, 165, 10.1016/0165-1218(90)90056-8 Bishop, 1980, The heritable translocation assay: its relationship to assessment of genetic risk for future generations, Teratogen. Carcinogen. Mutagen., 1, 305, 10.1002/tcm.1770010307 Bochkov, 1986, Cytogenetic effects of cyclophosphamide on human lymphocytes in vivo and in vitro, Mutation Res., 159, 103, 10.1016/0027-5107(86)90118-1 Bosbee, 1972, Aryl hydrocarbon hydroxylase in human leukocytes, Science, 178, 315, 10.1126/science.178.4058.315 Boyd, 1986, Nuclear magnetic resonance spectroscopic observation of the intracellular transformations of oncostatic cyclophosphamide metabolites, J. Med. Chem., 29, 1206, 10.1021/jm00157a015 Braun, 1986, Transplacental genetic and cytogenetic effects of alkylating agents in the mouse. II. Induction of chromosomal aberrations, Teratogen. Carcinogen. Mutagen., 6, 69, 10.1002/tcm.1770060108 Brock, 1987, Development of an intact hepatocyte activation system for routine use with the mouse lymphoma assay, Environ. Mutagen., 9, 331, 10.1002/em.2860090312 Brock, 1971, Activation of cyclophosphamide in man and animals, Cancer, 27, 1512, 10.1002/1097-0142(197106)27:6<1512::AID-CNCR2820270636>3.0.CO;2-Q Brookes, 1961, The alkylation of guanosine and guanylic acid, J. Chem. Soc., 766, 3923, 10.1039/jr9610003923 Burke, 1977, 3-Methylcholanthrene induces monooxygenase (O-deethylation) activity of human lymphocytes, Cancer Res., 37, 460 Cacheiro, 1974, Translocations the predominant cause of total sterility in sons of mice treated with mutagens, Genetics, 76, 73, 10.1093/genetics/76.1.73 Calabresi, 1985, Chemotherapy of neoplastic diseases, 1240 Cannon, 1991, Cyclophosphamide-associated carcinoma of urothelium: modalities for prevention, Urology, 38, 413, 10.1016/0090-4295(91)80228-Y Chang, 1993, Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes, Cancer Res., 53, 1 Channarayappa, 1990, Micronuclei assay in cytokinesis-blocked binucleated and conventional mononucleated methods in human peripheral lymphocytes, Teratogen. Carcinogen. Mutagen., 10, 273, 10.1002/tcm.1770100310 Chetsanga, 1982, Analysis and excision of ring-opened phosphoramide mustarddeoxyguanine adducts in DNA, Cancer Res., 42, 2616 Cholerton, 1992, The role of individual cytochromes P450 in drug metabolism and clinical response, Trends Pharmacol. Sci., 13, 434, 10.1016/0165-6147(92)90140-2 Chrisman, 1979, Cytogenetic effects of diethylstilbestrol-diphosphate (Des-dp) on mouse bone marrow monitored by the micronucleus test, Mutation Res., 67, 157, 10.1016/0165-1218(79)90126-5 Chrisman, 1980, Micronuclei in bone-marrow cells of mice subjected to hyperthermia, Mutation Res., 77, 95, 10.1016/0165-1218(80)90125-1 Clermont, 1972, Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal, Physiol. Rev., 52, 198, 10.1152/physrev.1972.52.1.198 Cole, 1983, Short-term tests for transplacentally active carcinogens. A comparison of sister-chromatid exchange and the micronucleus test in mouse foetal liver crythroblasts, Mutation Res., 113, 61, 10.1016/0165-1161(83)90241-8 Cooper, 1992, Immunoaffinity purification combined with 32P-postlabeling for the detection of O6-methylguanine in DNA from human tissues, Carcinogenesis, 13, 469, 10.1093/carcin/13.3.469 Cox, 1979, Cyclophosphamide cystitis — identification of acrolein as the causative agent, Biochem. Pharmacol., 28, 2045, 10.1016/0006-2952(79)90222-3 Cranz, 1976, Effect of short-term cyclophosphamide administration on rabbit sperm, C.R. Scanc. Soc. Biol., 170, 1289 Crook, 1986, Cytotoxicity, DNA cross-linking, and single strand breaks induced by activated cyclophosphamide and acrolein in human leukemia cells, Cancer Res., 46, 5029 Cumming, 1971, Genetic effects of cyclophosphamide in the germ cells of male mice, Genetics., 68 da Cunha, 1982, Temporary effects of AMSA (4′-(9-acridinylamino) methanesulfon-m-anisidide chemotherapy on spermatogenesis, Cancer, 49, 2459, 10.1002/1097-0142(19820615)49:12<2459::AID-CNCR2820491207>3.0.CO;2-Q Darroudi, 1993, Metabolic activation of chemicals to mutagenic carcinogens by human hepatoma microsomal extracts in Chinese hamster ovary cells (in vitro), Mutagenesis, 8, 11, 10.1093/mutage/8.1.11 Datta, 1970, The effect of chemical mutagens on the mitotic chromosomes of the mouse, in vivo, 194 Dean, 1981, Mutagenicity of selected chemicals in the mammalian dominant lethal assay Dearfield, 1983, Evaluation of a human hepatoma cell line as a target cell in genetic toxicology, Mutation Res., 108, 437, 10.1016/0027-5107(83)90138-0 Dearfield, 1985, In vitro assays of in vivo exposure to cyclophosphamide: Induction of sister-chromatid exchanges in peripheral lymphocytes, bone-marrow cells and in cultured cells exposed to plasma, Mutation Res., 158, 97, 10.1016/0165-1218(85)90103-X Deknudt, 1982, Mutagenicity tests with nickel salts in the male mouse, Toxicol., 25, 289, 10.1016/0300-483X(82)90106-8 Deknudt, 1983, Influence of various mitogens on the yield of sister-chromatid exchanges, induced by chemicals, in human lymphocytes, Mutation Res., 111, 161, 10.1016/0027-5107(83)90060-X Dellarco, 1985, Special committee report, Part I: An evaluation of current testing approaches for the detection of chemically induced aneuploidy, 445 D'Incalci, 1979, Decreased half-life of cyclophosphamide in patients under continual treatment, Eur. J. Cancer, 15, 7, 10.1016/0014-2964(79)90198-1 Dobos, 1974, Cyclophosphamide-induced chromosomal aberrations in nontumorous patients, Humangenetik, 22, 221 Doehmer, 1990, Genetically engineered V79 Chinese hamster cells metabolically activate the cytostatic drugs cyclophosphamide and ifosfamide, Environ. Health Perspect., 88, 83, 10.1289/ehp.908863 Dooley, 1982, Biliary elimination of cyclophosphamide in man, Cancer Chemother. Pharmacol., 9, 26, 10.1007/BF00296757 DuFrain, 1979, Cyclophosphamide induced SCEs in rabbit lymphocytes, Environ. Mutagen., 1, 283, 10.1002/em.2860010311 Düker, 1981, Investigations into sister chromatid exchanges in patients under cytostatic therapy, Hum. Genet., 58, 198, 10.1007/BF00278711 Egorin, 1989, A limited sampling strategy for cyclophosphamide pharmacokinetics, Cancer Res., 49, 3129 Ehling, 1982, Risk estimations based on germ-cell mutations in mice, 709 Ehling, 1988, Induction of specific-locus and dominant-lethal mutations by cyclophosphamide and combined cyclophosphamide-radiation treatments, Mutation Res., 199, 21 Ehling, 1982, Dominant cataract mutations and specific locus mutations in mice induced by radiation or ethylnitrosourea, Mutation Res., 92, 181, 10.1016/0027-5107(82)90222-6 Eibs, 1977, Inhibition of post-implantation development of mouse blastocysts in vitro after cyclophosphamide treatments in vivo, Nature, 270, 54, 10.1038/270054a0 Elespuru, 1983, Biochemical prophage inducation assay: a rapid test for antitumor agents that interact with DNA, Cancer Res., 43, 2819 Epstein, 1972, Detection of chemical mutagens by the dominant lethal assay in the mouse, Toxicol. Appl. Pharmacol., 23, 288, 10.1016/0041-008X(72)90192-5 Erlichman, 1992, Pharmacology of anticancer drugs, 317 Escalante, 1989, Acute myelocytic leukemia after the use of cyclophosphamide in the treatment of polyarteritis nodosa, J. Rheumatol., 16, 1147 Fabricant, 1983, Postmeiotic cell mediation of behaviour in progeny of male rats treated with cyclophosphamide, Mutation Res., 119, 185, 10.1016/0165-7992(83)90127-6 Fahrig, 1977, The mammalian spot test (Fellfleckentest) with mice, Arch. Toxicol., 38, 87, 10.1007/BF00293666 Fairchild, 1979, The incidence of bladder cancer after cyclophosphamide therapy, J. Urol., 122, 163, 10.1016/S0022-5347(17)56306-5 Farmer, 1988, Enantiomers of cyclophosphamide amd iphosphamide, Biochem. Pharmacol., 37, 145, 10.1016/0006-2952(88)90767-8 Francis, 1990, Tumours and malformations in the adult offspring of cyclophosphamide-treated and control male rats — Preliminary communication, Mutation Res., 229, 239, 10.1016/0027-5107(90)90097-N Fritz, 1973, Embryolethality in the mouse following treatment of males with cyclophosphamide at specific germ cell stages, Agents Actions, 3, 35, 10.1007/BF02023849 Furukawa, 1978, Sister chromatid exchanges induced by cyclophosphamide in V79 cells cultured in difusion chambers in mice, Mutation Res., 57, 233, 10.1016/0027-5107(78)90273-7 Gad-El-Karim, 1984, Modifications in the myeloclastogenic effect of benzene in mice with toluene, phenobarbital, 3-methylcholanthrene, Aroclor 1254 and SKF-525A, Mutation Res., 135, 225, 10.1016/0165-1218(84)90126-5 Galloway, 1985, Development of a standard protocol for in vitro cytogenetic testing with Chinese hamster ovary cells: comparison of results for 22 compounds in two laboratories, Environ. Mutagen., 7, 1, 10.1002/em.2860070102 Garner, 1985, Assessment of carcinogen exposure in man, Carcinogenesis, 6, 1071, 10.1093/carcin/6.8.1071 Gebhart, 1985, The action of anticlastogens in human lymphocyte cultures and their modification by rat-liver S9 mix, Mutation Res., 149, 83, 10.1016/0027-5107(85)90012-0 Generoso, 1978, Inducibility by chemical mutagens of heritable translocations in male and female germ cells of mice, Vol. 5, 109 Generoso, 1981, Mutagenicity of selected chemicals in mammals: the heritable translocation test, 681 Generoso, 1990, Developmental anomalies: Mutational consequences of mouse zygote exposure, 311 Ghaskadbi, 1992, Modulation of cyclophosphamide mutagenicity by vitamin C in the in vivo rodent micronucleus assay, Teratogen. Carcinogen. Mutagen., 12, 11, 10.1002/tcm.1770120103 Gibbons, 1988, Acute non-lymphocytic leukaemia following short-term, intermittent, intravenous cyclophosphamide treatment of lupus nephritis, Arthritis Rheum., 31, 1552, 10.1002/art.1780311212 Goetz, 1975, Relationship between experimental results in mammals and man. I. Cytogenetic analysis of bone marrow injury induced by a single dose of CO, Mutation Res., 31, 247, 10.1016/0165-1161(75)90007-2 Goetz, 1980, Cyclophosphamide-induced chromosomal aberrations in meiotic cells of male mice, Folia Biol. (Praha), 26, 289 Goldberg, 1983, Comparison of the effects of 1,2-dimethylhydrazine and cyclophosphamide on micronucleus incidence in bone marrow and colon, Mutation Res., 109, 91, 10.1016/0027-5107(83)90098-2 Graf, 1989, Thirty compounds tested in the Drosophila wing spot test, Mutation Res., 222, 359, 10.1016/0165-1218(89)90112-2 Graham, 1983, Decreased plasma half-life of cyclophosphamide during repeated high-dose administration, Cancer Chemother. Pharmacol., 10, 192, 10.1007/BF00255760 Graham, 1991, Drug metabolism in carcinogenesis and cancer chemotherapy, Pharmac. Ther., 51, 275, 10.1016/0163-7258(91)90083-X Hadidi, 1988, Phenotypically deficient elimination of carboxyphosphamide after cyclophosphamide administration to cancer patients, Cancer Res., 48, 5167 Hales, 1990, Reversibility of the effects of chronic paternal exposure to cyclophosphamide on pregnancy outcome in rats, Mutation Res., 229, 129, 10.1016/0027-5107(90)90087-K Hales, 1992, Increased postimplantation loss and malformations among the F2 progeny of male rats chronically treated with cyclophosphamide, Teratology, 45, 671, 10.1002/tera.1420450612 Hampel, 1966, The action of cytostatic agents on the chromosomes of human leukocytes in vitro, Blood, 27, 816, 10.1182/blood.V27.6.816.816 Hansmann, 1974, Chromosome aberrations in metaphase II oocytes: Stage sensitivity in the mouse oogenesis to amethopterin and cyclophosphamide, Mutation Res., 22, 175, 10.1016/0027-5107(74)90098-0 Harris, 1985, Future directions in the use of DNA adducts as dosimeters for monitoring human exposure to environmental mutagens and carcinogens, Environ. Health Perspect., 62, 185, 10.1289/ehp.8562185 Hart, 1983, Induction of micronuclei in the mouse, Revised timing of the final stage of erythropoiesis, Mutation Res., 120, 127, 10.1016/0165-7992(83)90153-7 Heddle, 1981, Comparative mutagenicity of myleran and cyclophosphamide, 893 Hemminki, 1985, Binding of metabolites of cyclophosphamide to DNA in a rat liver microsomal system and in vivo in mice, Cancer Res., 45, 4237 Ho, 1981, Screening of carcinogens with the prophage lambdaclts857 induction test, Cancer Res., 41, 532 Hohorst, 1976, The problem of oncostatic specificity of cyclophosphamide, Cancer Treat. Rep., 60, 309 Honjo, 1988, Hepatotoxicity of cyclophosphamide in man: pharmacokinetic analysis, Res. Commun. Chem. Path. Pharmacol., 61, 149 Huang, 1980, An in vitro metabolic activation assay using liver microsomes in diffusion chambers: induction of sister chromatid exchanges and chromosome aberrations by cyclophosphamide or ifosfamide in cultured human and Chinese hamster cells, Carcinogenesis, 1, 37, 10.1093/carcin/1.1.37 Hugenholtz, 1979, Radiation-induced heritable sperm abnormalities in mice, Environ. Mutagen., 1, 127 Hutter, 1982, Rapid detection of mutagen induced micronucleated erythrocytes by flow cytometry, Histochemistry, 75, 353, 10.1007/BF00496738 Huttner, 1992, Analysis of HPRT-deficient lymphocytes in mouse (spleen) and man (peripheral blood), Mutagenesis, 7, 160 IARC, 1981, 165 IARC, 1987, 182 Ikeuchi, 1981, Differential inducibility of chromosome aberrations and sister-chromatid exchanges by indirect mutagens in various mammalian cell lines, Mutation Res., 90, 149, 10.1016/0165-1218(81)90078-1 Inoue, 1980, Induction of sister chromatid exchanges by cyclophosphamide in human lymphocytes with metabolic activation, 56, 568 Inskeep, 1971, Effect of cyclophosphamide in rams, J. Anim. Sci., 33, 1022, 10.2527/jas1971.3351022x Ioan, 1977, The mutagenic effect of 131I and of two cytostatics revealed by the micronucleus test (MT), Rev. Roum. Med. Endocrinol., 15, 119 Jacquet, 1984, Morphological and cytogenetic studies of dominant lethality induced by mitomycin C and cyclophosphamide in female germ cells, Mutation Res., 138, 181, 10.1016/0027-5107(84)90106-4 James, 1982, Analysis of results from a collaborative study of the dominant lethal assay, Mutation Res., 97, 303, 10.1016/0165-1161(82)90029-2 Jao, 1972, Phenobarbital effects on cyclophosphamide pharmacokinetics in man, Cancer Res., 32, 2761 Jenkinson, 1990, Malformed foetuses and karyotype abnormalities in the offspring of cyclophosphamide and allyl alcohol-treated male rats, Mutation Res., 229, 173, 10.1016/0027-5107(90)90091-H Jenkinson, 1987, Increased incidence of abnormal foetuses in the offspring of cyclophosphamide-treated male mice, Mutation Res., 188, 57, 10.1016/0165-1218(87)90115-7 Johnson, 1981, Electrophoretically detected germinal mutations induced in the mouse by ethylnitrosourea, 78, 3138 Jones, 1987, Factors that affect the frequency of thioguanine-resistant lymphocytes in mice following exposure to ethylnitrosoures, Environ. Mutagen., 9, 317, 10.1002/em.2860090311 Juma, 1979, First pass hepatic metabolism of cyclophosphamide, Br. J. Clin. Pharmacol., 1, 422, 10.1111/j.1365-2125.1979.tb00967.x Kallama, 1984, Alkylation of guanosine by phosphoramide mustard, chloromethane hydrochloride and chlorambucil, Acta Pharmacol. Toxicol., 54, 214, 10.1111/j.1600-0773.1984.tb01920.x King, 1979, Transplacental mutagenesis: The micronucleus test on fetal mouse blood, Hum. Genet., 51, 183, 10.1007/BF00287174 Kinlen, 1985, Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatment, Am. J. Med., 78, 44, 10.1016/0002-9343(85)90245-1 Knudsen, 1980, The mammalian spot test and its use for the testing of potential carcinogenicity of welding fume particles and hexavalent chromium, Acta Pharmacol. Toxicol., 47, 66, 10.1111/j.1600-0773.1980.tb02027.x Knudsen, 1977, A proposed method for the simultaneous detection of germ-cell mutations leading to fetal death (dominant lethality) and of malformations (male teratogenicity) in mammals, Mutation Res., 48, 267, 10.1016/0027-5107(77)90168-3 Kohler, 1991, Analysis of spontaneous and induced mutations in transgenic mice using a lambda ZAPlacI shuttle vector, Environ. Mol. Mutagen., 18, 316, 10.1002/em.2850180421 Korte, 1980, Chromosomal analysis in bone-marrow cells of Chinese hamsters after treatment with mycotoxins, Mutation Res., 78, 41, 10.1016/0165-1218(80)90024-5 Krishna, 1987, Cyclophosphamide-induced cytogenetic effects in mouse bone marrow and spleen cells in in vivo and in vivo/in vitro assays, Teratogen. Carcinogen. Mutagen., 7, 183, 10.1002/tcm.1770070209 Krishna, 1989, Use of the cytokinesis-block method for the analysis of micronuclei in V79 Chinese hamster lung cells: results with mitomycin C and cyclophosphamide, Mutation Res., 222, 63, 10.1016/0165-1218(89)90036-0 Krishna, 1991, Simultaneous micronucleus and chromosome aberration assessment in the rat, Mutation Res., 264, 29, 10.1016/0165-7992(91)90042-3 Kugler, 1987, The effectiveness of S9 and microsomal mix on activation of cyclophosphamide to induce genotoxicity in human lymphocytes, Mutation Res., 187, 151, 10.1016/0165-1218(87)90082-6 Lähdetie, 1983, Micronuclei induced during meiosis by ethyl methanesulfonate, cyclophosphamide and dimethyl-benzanthracene in male rats, Mutation Res., 120, 257, 10.1016/0165-7992(83)90098-2 Lähdetie, 1988, Induction and survival of micronuclei in rat spermatids. Comparison of two meiotic micronucleus techniques using cyclophosphamide, Mutation Res., 203, 47, 10.1016/0165-1161(88)90007-6 Lähdetie, 1990, Interaction of mesna (2-mercaptoethane sulfonate) with the mutagenicity of cyclophosphamide in vitro and in vivo, Mutation Res., 245, 27, 10.1016/0165-7992(90)90021-B LeBlanc, 1989, Interaction of anti-cancer drugs with hepatic monooxygenase enzymes, Drug Metab. Rev., 20, 395, 10.3109/03602538909103550 Le Curieux, 1993, Comparison of three short-term assays: results on seven chemicals, potential contribution to the control of water genotoxicity, Mutation Res., 319, 223, 10.1016/0165-1218(93)90082-O Léonard, 1972, Observation of dividing spermatocytes for chromosome aberrations induced in mouse spermatogonia by chemical mutagens, Mutation Res., 16, 297, 10.1016/0027-5107(72)90160-1 Léonard, 1983, Cytotoxicologie. Comparaison, in vivo, des propriétés clastogéniques du busulfan et du cyclophosphamide, C.R. Soc. Biol., 177, 239 Liang, 1985, Chemical probes and possible targets for the induction of aneuploidy, 491 Loeb, 1986, Mutagenesis by apurinic/apyrimidinic sites, Annu. Rev. Genet., 20, 201, 10.1146/annurev.ge.20.120186.001221 Maccubbin, 1991, A cyclophosphamide-DNA phosphoester adduct formed in vitro and in vivo, Cancer Res., 51, 886 MacGregor, 1980, Clastogen-induced micronuclei in peripheral bood erythrocytes: The basis of an improved micronucleus test, Environ. Mutagen., 2, 509, 10.1002/em.2860020408 Machemer, 1975, Experiences with the dominant lethal test in female mice: Effects of alkylating agents and artificial sweeteners on pre-ovulatory oocyte stages, Mutation Res., 29, 209, 10.1016/0027-5107(75)90134-7 Machemer, 1975, Method for testing mutagenic effects of chemicals on spermatogonia of the Chinese hamster, Arzneim.-Forsch. (Drug Res.), 25, 1889 Machemer, 1976, Evaluation of the mutagenic potential of cyclohexylamine on spermatogonia of the Chinese hamster, Mutation Res., 40, 243, 10.1016/0165-1218(76)90050-1 Machemer, 1978, Mutagenicity studies with praziquantel, a new anthelmintic drug, in mammalian systems, Arch. Toxicol., 39, 187, 10.1007/BF00368227 Madle, 1981, Evaluation of experimental parameters in an S9/human leukocyte SCE test with cyclophosphamide, Mutation Res., 85, 347, 10.1016/0165-1161(81)90225-9 Madle, 1977, In vitro testing of indirect mutagen (CP) with human leukocytes culture. Activation with liver microsomes and use of dialysis bag, Mutation Res., 56, 101, 10.1016/0027-5107(77)90250-0 Madle, 1978, In vitro testing of an indirect mutagen (cyclophosphamide) with human leukocyte cultures. Activation by a non-enzymatic hydroxylation system (Udenfriend system), Mutation Res., 49, 149, 10.1016/0027-5107(78)90088-X Madle, 1978, Testing in vitro of an indirect mutagen (cyclophosphamide) with human leukocyte cultures. Activation by liver perfusion and by incubation with crude liver homogenate, Mutation Res., 51, 95, 10.1016/0165-1161(78)90139-5 Maier, 1976, Ten model mutagens evaluated by the micronucleus test, Mutation Res., 40, 325, 10.1016/0165-1218(76)90031-8 Malashenko, 1984, Specific sensitivity of inbred mouse strains TPS, WR, and CBALacY to chemical mutagens, 1141 Mamber, 1986, The Escherichia coli K-12 SOS chromotest agar spot test for simple, rapid detection of genotoxic agents, Mutation Res., 171, 83, 10.1016/0165-1218(86)90039-X Marinello, 1984, Metabolism and binding of cyclophosphamide and its metabolite acrolein to rat hepatic microsomal cytochrome P-450, Cancer Res., 44, 4615 Martin, 1977, Measurement of ‘unscheduled’ DNA synthesis in HeLa cells by liquid scintillation counting after carcinogen treatment, Cancer Lett., 2, 355, 10.1016/S0304-3835(77)80017-7 Martin, 1978, Testing of known carcinogens and noncarcinogens for their ability to induce unscheduled DNA synthesis in HeLa cells, Cancer Res., 38, 2621 Masuda, 1990, Cytochrome P-450 and chromosome damage by cyclophosphamide in LEC strain rats predisposed to hereditary hepatitis and liver cancer, Mutation Res., 244, 309, 10.1016/0165-7992(90)90078-X Mauss, 1972, Influence of cytostatic therapy on andrologic findings, Arch. Dermatol. Forsch., 244, 437, 10.1007/BF00600239 McDiarmid, 1990, Baseline and phosphoramide mustard-induced sister-chromatid exchanges in cancer patients treated with cyclophosphamide, Mutation Res., 241, 273, 10.1016/0165-1218(90)90024-V McDiarmid, 1992, Baseline and phosphoramide mustard-induced sister-chromatid exchanges in pharmacists handling anti-cancer drugs, Mutation Res., 279, 199, 10.1016/0165-1218(92)90067-A Mehta, 1982, Trapping of DNA-reactive metabolites of therapeutic or carcinogenic agents by carbon-14-labelled synthetic polynucleotides, Cancer Res., 42, 2996 Mehta, 1980, Alkylation of guanosine and deoxyguanosine by phosphoramide mustard, Cancer Res., 40, 4183 Migliore, 1989, The human lymphocyte micronucleus assay: a comparison between whole-blood and separated-lymphocyte cultures, Mutation Res., 227, 167, 10.1016/0165-7992(89)90041-9 Miltenburger, 1981, Differential chromosomal damage in Chinese hamster bone-marrow cells and in spermatogonia after mutagenic treatment, Mutation Res., 81, 117, 10.1016/0027-5107(81)90092-0 Mirkes, 1992, Identification of cyclophosphamide-DNA adducts in rat embryos in vitro to 4-hydroxyperoxy-cyclophosphamide, Chem. Res. Toxicol., 5, 382, 10.1021/tx00027a010 Mitchell, 1981, Analysis of in vivo results of cyclophosphamide-induced chromosomal damage in mammals from sensitivity and statistical aspects, J. Toxicol. Environ. Health, 7, 585, 10.1080/15287398109530003 Mohn, 1976, Genetic effects of cyclophosphamide, ifosfamide and trofosfamide, Mutation Res., 32, 331, 10.1016/0165-1110(76)90005-1 Monaco, 1992, Mutagenicity of methyl methanesulfonate and cyclophosphamide in resting and growing Saccharomyces cerevisiae D7 cells, Mutation Res., 282, 235, 10.1016/0165-7992(92)90128-5 Moore, 1991, Clinical pharmacokinetics of cyclophosphamide, Clin. Pharmacokinet., 20, 194, 10.2165/00003088-199120030-00002 Morad, 1977, Non-random distribution of cyclophosphamide-induced chromosome breaks, Mutation Res., 42, 125, 10.1016/S0027-5107(77)80015-8 Moreland, 1981, Effects of prolonged chemical treatment with cyclophosphamide and 6-mercaptopurine in the dominant lethal test system, Mutation Res., 90, 193, 10.1016/0165-1218(81)90082-3 Moses, 1985, The synaptonemal complex in meiosis: Significance of induced perturbations, 337 Mukherjee, 1991, Effect of ‘pan masala’ on the germ cells of male mice, Cancer Lett., 58, 161, 10.1016/0304-3835(91)90095-Y Mulvihill, 1993, Genetic counseling of the cancer patient, 2529 Mulvihill, 1985, Offspring of long-time survivors of childhood cancer, Clin. Oncol., 4, 333 Musilova, 1979, Sister-chromatid exchanges and chromosal breakage in patients treated with cytostatics, Mutation Res., 67, 289, 10.1016/0165-1218(79)90023-5 Myhr, 1991, Validation studies with Muta™ Mouse: a transgenic mouse model for detecting mutations in vivo, Environ. Mol. Mutagen., 18, 308, 10.1002/em.2850180420 Nau, 1982, Mutagenic, teratogenic and pharmacokinetic properties of cyclophosphamide and some of its deuterated derivatives, Mutation Res., 95, 105, 10.1016/0027-5107(82)90250-0 Neda, 1977, In vivo cytogenetic studies of 10-chloro-11b-(2-fluorophenyl)-7-(2-hydroxyethyl)-2,3,5,11b-tetrahydrooxazolo-[3,2-d] [1,4] benzodiazepine-6(7H)-one (MS-4101) on rat bone marrow cells, Folia Pharmacol. Japon., 73, 651, 10.1254/fpj.73.651 Neistadt, 1976, Effect of chemotherapy on the lymph node and bone marrow cell chromosomes in patients with Hodgkin's disease, Neoplasms, 25, 91 Newman, 1990, Mutagenesis assays on urines produced by patients administered adriamycin and cyclophosphamide, Environ. Mol. Mutagen., 16, 189, 10.1002/em.2850160307 Nguyen, 1982, Exposure of pharmacy personnel to mutagenic antineoplastic drugs, Cancer Res., 42, 4792 Norppa, 1983, Metabolic activation of styrene by erythrocytes detected as increased sister chromatid exchanges in cultured human lymphocytes, Cancer Res., 43, 3579 Oakberg, 1983, Germ cell toxicity: significance in genetic and fertility effects of radiation and chemicals, 549 Oesch-Bartlomowicz, 1990, Modulation of the control of mutagenic metabolites derived from cyclophosphamide and ifosfamide by stimulation of protein kinase A, Mutation Res., 232, 305, 10.1016/0027-5107(90)90137-S Oglesby, 1989, Induced hepatocytes as a metabolic activation system for the mouse-lymphoma assay, Mutation Res., 223, 295, 10.1016/0165-1218(89)90122-5 Ortiz, 1992, Bladder cancer after cyclophosphamide therapy for lupus nephritis, Nephron, 60, 378, 10.1159/000186790 Ostrosky-Wegman, 1986, Susceptibility to genotoxic effects of niclosamide in human peripheral lymphocytes exposed in vitro and in vivo, Mutation Res., 173, 81, 10.1016/0165-7992(86)90015-1 Pacchierotti, 1983, Cytogenetic observations in mouse secondary spermatocytes on numerical and structural chromosome aberrations induced by cyclophosphamide in various stages of spermatogenesis, Mutation Res., 119, 177, 10.1016/0165-7992(83)90126-4 Paik, 1977, Genetic effects of pesticides in the mammalian cells. I. Induction of micronucleus, Korean J. Zool., 20, 19 Patel, 1990, Metabolism and pulmonary toxicity of cyclophosphamide, Pharmac. Ther., 47, 137, 10.1016/0163-7258(90)90049-8 Pedersen-Bjergaard, 1988, Carcinoma of the urinary bladder after treatment with cyclophosphamide for non-Hodgkin's lymphoma, New Engl. J. Med., 318, 1028, 10.1056/NEJM198804213181604 Peter, 1980, Inducibility of somatic colour and white spots in the mammalian spot test, Mutation Res., 70, 103, 10.1016/0027-5107(80)90062-7 Pomerantseva, 1981, Comparative efficacy of different tests for determining the mutagenicity of certain factors in mammals, II. Frequency of abnormal sperm heads in mice exposed to various factors, Genetika, 16, 1397 Qiu, 1992, Adverse effects of cyclophosphamide on progeny outcome can be mediated through post-testicular mechanisms in the rat, Biol. Reprod., 46, 926, 10.1095/biolreprod46.5.926 Ramaiya, 1980, Comparative effectiveness of the use of various tests for the determination of mutagenicity of certain factors in mammals. I. Frequency of dominant lethal mutations and chromosome aberrations in mouse bone marrow cells, induced by N-nitrosomorpholine, N-nitroso-N-methylurea, and cyclophosphamide, 662 Randerath, 1981, 32P-post-labeling test for DNA damage, 78, 6126 Raposa, 1978, Sister chromatid exchange studies for monitoring DNA damage and repair capacity after cytostatics in vitro and in lymphocytes of leukaemic patients under cytostatic therapy, Mutation Res., 57, 241, 10.1016/0027-5107(78)90274-9 Raposa, 1984, SCE induction by cytostatics and its relation to iatrogenic leukemogenesis, Basic Life Sci., 29, 859 Rathenberg, 1975, Cytogenetic effects of cyclophosphamide on mouse spermatogonia, Humangenetik, 29, 135, 10.1007/BF00430350 Rathenberg, 1972, Comparative cytogenetic studies of the influence of phenylbutazone and cyclophosphamide on spermatogenesis in the mouse, Agents Actions, 2, 180, 10.1007/BF01965857 Rhomberg, 1990, Quantitative estimation of the genetic risk associated with the induction of heritable translocations at low-dose exposure: ethylene oxide as an example, Environ. Mol. Mutagen., 16, 104, 10.1002/em.2850160208 Richardson, 1982, An assessment of clastogenic potential of 4-chloromethylbiphenyl in human lymphocytes in vitro, Mutation Res., 100, 287, 10.1016/0165-1218(82)90062-3 Roberts, 1978, The dominant lethal effects of some ergot alkaloids, Mutation Res., 50, 317, 10.1016/0027-5107(78)90037-4 Röhrborn, 1970, The activity of alkylating agents: I. Sensitive mutable stages in spermatogenesis and oogenesis, 294 Röhrborn, 1971, Induced chromosome aberrations in unfertilized oocytes of mice, Humangenetik, 13, 184, 10.1007/BF00326941 Röhrborn, 1976, Investigations on the frequency of chromosome aberrations in bone marrow cells of Chinese hamsters after simultaneous application of caffeine and cyclophosphamide, Hum. Genet., 33, 113, 10.1007/BF00281885 Röhrborn, 1977, Cytogenetic investigations of mammals, comparison of the genetic activity of cytostatics in mammals, Arch. Toxicol., 38, 35, 10.1007/BF00293661 Rossi, 1983, Genotoxicity, metabolism and blood kinetics of epichlorohydrin in mice, Mutation Res., 118, 213, 10.1016/0165-1218(83)90144-1 Rössner, 1979 Roszinsky-Köcher, 1979, Effects of various cyclophosphamide concentrations in vivo on sister chromatid exchanges (SCE) and chromosome aberrations of Chinese hamster bone marrow cells, Hum. Genet., 46, 51, 10.1007/BF00278901 Russell, 1981, The mouse specific-locus test with agents other than radiations: interpretations of data and recommendations for future work, Mutation Res., 86, 329, 10.1016/0165-1110(81)90010-5 Russell, 1990, Factors affecting the nature of induced mutations, 271 Rutledge, 1992, Developmental anomalies derived from exposure of zygotes and first-cleavage embryos to mutagens, Mutation Res., 296, 167, 10.1016/0165-1110(92)90040-G Salamone, 1981, Mutagenic activity of 41 compounds in the in vivo micronucleus assay, Vol. 1, 686 Salamone, 1982, On the complexities of risk estimates, metabolic activation, and chemical mixtures, Progress in Mutation Res., Vol. 3, 179 Salvadori, 1992, The protective effect of β-carotene on genotoxicity induced by cyclophosphamide, Mutation Res., 265, 237, 10.1016/0027-5107(92)90052-4 Santella, 1988, Application of new techniques for the detection of carcinogen adducts to human population, Mutation Res., 205, 271, 10.1016/0165-1218(88)90022-5 Sbrana, 1984, Human lymphocytes assay: Cyclophosphamide metabolic activation by S9 system with low cytotoxicity, Mutation Res., 130, 411, 10.1016/0165-1161(84)90013-X Schlegel, 1983, A rapid screen for cumulative chromosomal damage in mice accumulation of circulating micronucleated erythrocytes, Mutation Res., 113, 481, 10.1016/0165-1161(83)90002-X Schmid, 1979, Unscheduled DNA synthesis in male rabbit germ cells induced by methylmethane sulfonate, cyclophosphamide and adriamycin, 503 Schmid, 1971, Chemical mutagenesis, The Chinese hamster bone marrow as an in vivo test system, I. Cytogenetic results on basic aspects of the methodology, obtained with alkylating agents, Humangenetik, 11, 103, 10.1007/BF00393791 Schuler, 1979, Chromosome mutations and chromosome stability in children treated with different regimes of immunosuppressive drugs, Hum. Hered., 29, 100, 10.1159/000153024 Searle, 1986, The role of dominant visibles in mutagenicity testing, Prog. Clin. Biol. Res., 209B, 511 Selby, 1990, The importance of the direct method of genetic risk estimation and ways to improve it, 437 Selby, 1984, Non breeding-test methods for dominant skeletal mutations shown by ethylnitrosourea to be easily applicable to offspring examined in specific locus tests experiments, Mutation Res., 127, 93, 10.1016/0027-5107(84)90144-1 Sharma, 1987, Effect of mitomycin-C and cyclophosphamide on the polytene chromosomes of Anopheles stephensi (Culicidae: Diptera), Cytobios, 52, 153 Shev, 1990, The feasibility of using Chinese hamsters as an animal model for aneuploidy, Environ. Mol. Mutagen., 16, 320, 10.1002/em.2850160412 Shindo, 1983, The micronucleus test with mouse spleen cells, Mutation Res., 121, 53, 10.1016/0165-7992(83)90086-6 Sigal, 1991, Carcinoma of bladder following long-term cyclophosphamide therapy, Arch. Pathol. Lab. Med., 115, 1049 Simula, 1992, Species differences in the genotoxicity of cyclophosphamide and styrene in three in vivo assays, Mutation Res., 271, 49, 10.1016/0165-1161(92)90031-G Skare, 1984, Alkaline elution of rat testicular DNA: Detection of DNA cross-links after in vivo treatment with chemical mutagens, Mutation Res., 130, 295, 10.1016/0165-1161(84)90105-5 Skinner, 1982, Unscheduled DNA synthesis detection and metaphase analysis in a common test system in vivo-in vitro, J. Appl. Toxicol., 2, 172, 10.1002/jat.2550020311 Smith, 1991, Cooxidation of cyclophosphamide as an alternative pathway for its bioactivation and lung toxicity, Cancer Res., 51, 542 Sobels, 1977, Some problems associated with the testing for environmental mutagens and a perspective for studies in comparative mutagenesis, Mutation Res., 46, 245, 10.1016/0165-1161(77)90001-2 Sobels, 1982, The parallelogram: An indirect approach for the assessment of genetic risks from chemical mutagens, Vol. 3, 323 Sorsa, 1982, Induction of sister chromatid exchanges among nurses handling cytostatic drugs, 341 Sorsa, 1988, Biological and environmental monitoring of occupational exposure to cyclophosphamide in industry and hospitals, Mutation Res., 204, 465, 10.1016/0165-1218(88)90042-0 Sotomayor, 1975, Induction of translocations by cyclophosphamide in different germ cell stages of male mice: Cytological characterization and transmission, Mutation Res., 27, 375, 10.1016/0027-5107(75)90295-X Sotomayor, 1978, Unscheduled DNA synthesis in spermatogenic cells of mice treated in vivo with the indirect alkylating agents cyclophosphamide and mitomen, Mutation Res., 50, 229, 10.1016/0027-5107(78)90027-1 Spielberg, 1984, In vitro assesment of pharmacogenetic susceptibility to toxic drug metabolites in human, 43, 2308 Srám, 1976, Relationship between acute and chronic exposures in mutagenicity studies in mice, Mutation Res., 41, 25, 10.1016/0027-5107(76)90071-3 Srám, 1981, Change in the frequency of chromosome aberrations in the bone marrow of mice examined at various intervals after a single dose or continuous exposure to cyclophosphamide, Folia Biol., 27, 58 Staiano, 1981, Lack of mutagenic activity in urine from hospital pharmacists admixing antitumor drugs, Lancet, 1, 615, 10.1016/S0140-6736(81)92064-X Stephan, 1978, Testing in vitro of an indirect mutagen (cyclophosphamide) with human leukocyte cultures: Activation by liver perfusion and by incubation with crude liver homogenate, Mutation Res., 51, 95 Stetka, 1976, Sister chromatid exchange as an assay for genetic damage induced by mutagencarcinogens. I. In vivo test for compounds requiring metabolic activation, Mutation Res., 41, 333, 10.1016/0027-5107(76)90106-8 Stetka, 1976, Sister chromatid exchange as an assay for genetic damage induced by mutagencarcinogens, II. In vitro test for compounds requiring metabolic activation, Mutation Res., 41, 343, 10.1016/0027-5107(76)90107-X Styles, 1983, A comparison of the incidence of micronuclei in blood and bone marrow in 3 strain of mouse dosed with cyclophosphamide or hexamethylphosphoramide (HMPA), Mutation Res., 122, 143, 10.1016/0165-7992(83)90052-0 Sykora, 1978, Dominant-lethal assay of selected cytostatics, Neoplasma, 25, 523 Sykora, 1979, Experiences with methods testing the mutagenic and antifertility effects of the model drug cyclophosphamide, 263 Tasso, 1992, Pharmacokinetics and metabolism of cyclophosphamide in paedriatic patients, Cancer Chemother. Pharmacol., 30, 207, 10.1007/BF00686313 Tates, 1992, Validation studies with the micronucleus test for early spermatids of rats. A tool for detecting clastogenicity of chemicals in differentiating spermatogonia and spermatocytes, Mutagenesis, 7, 411, 10.1093/mutage/7.6.411 Thrasher, 1990, Bladder leiomyosarcoma following cyclophosphamide therapy for lupus nephritis, J. Urol., 143, 119, 10.1016/S0022-5347(17)39886-5 Timourian, 1983, Sperm shape abnormalities in the offspring of male mice treated with triethylenemelamine (TEM), Environ. Mutagen., 5, 399 Topham, 1980, Chemically induced transmissible abnormalities in sperm-head shape, Mutation Res., 70, 109, 10.1016/0027-5107(80)90063-9 Topham, 1980, The detection of carcinogen-induced sperm head abnormalities in mice, Mutation Res., 69, 149, 10.1016/0027-5107(80)90184-0 Topinková, 1982, Cytogenetic examination of bone marrow cells and peripheral lymphocytes in rats exposed to cyclophosphamide, Folia Biol. (Phraha), 28, 302 Trasler, 1985, Paternal cyclophosphamide treatment of rats causes fetal loss and malformations without affecting male fertility, Nature, 316, 144, 10.1038/316144a0 Travis, 1989, Bladder cancer after chemotherapy for non-Hodgkin's lymphoma, New Engl. J. Med., 321, 544, 10.1056/NEJM198908243210815 Trosko, 1974, A sensitive method to measure ‘unscheduled DNA synthesis’ in rapidly dividing eukaryotic cells, Exp. Cell Res., 88, 47, 10.1016/0014-4827(74)90616-8 Tsuchimoto, 1981, Activity of coded compounds in the micronucleus test, Vol. 1, 686 Tucker, 1993, Sisterchromatid exchange: second report of the gene-toxprogram, Mutation Res., 297, 101, 10.1016/0165-1110(93)90001-4 UNSCEAR, 1993, Annex G. Hereditary effects of radiation, 729 Vanparys, 1982, Mutagenicity tests with astemizole in vitro and in vivo, Arch. Toxicol., 50, 167, 10.1007/BF00373399 Venier, 1989, Induction of SOS response in Escherichia coli strain PQ37 by 16 chemical compounds and human urine extracts, Mutagenesis, 4, 51, 10.1093/mutage/4.1.51 Vigil, 1985, Alkylating agents and mouse spermatogenesis: Effects of a single dose of cyclophosphamide, Andrologia, 17, 276, 10.1111/j.1439-0272.1985.tb01002.x Vijayalaxmi, 1979, Induction of sisterchromatid exchanges in human lymphocytes and Chinese hamster cells exposed to aflatoxin B1 and N-methyl-N-nitrosourea, Mutation Res., 67, 47, 10.1016/0165-1218(79)90098-3 Vogel, 1993, Performance of 181 chemicals in a Drosophila assay predominantly monitoring interchromosomal mitotic recombination, Mutagenesis, 8, 57, 10.1093/mutage/8.1.57 Voiculetz, 1982, Comparative studies of three mutagenicity carcinogenicity tests using cyclophosphamide and benzo[a]pyrene, Oncologia, 21, 33 Von der Hude, 1988, Evaluation of the SOS chromotest, Mutation Res., 203, 81, 10.1016/0165-1161(88)90023-4 Vu, 1981, Identification of three alkylated nucleotide adducts from the reaction of guanosine-5′-monophosphate with phosphoramide mustard, J. Am. Chem. Soc., 103, 7362, 10.1021/ja00414a067 Waalkens, 1981, Sister-chromatid exchanges induced in vitro by cyclophosphamide without exogenous metabolic activation in lymphocytes from three mammalian species, Toxicol. Lett., 7, 229, 10.1016/0378-4274(81)90073-4 Waxman, 1993, Interactions of Anti-Cancer Drugs with Cytochromes P450 and Glutatione S-Transferases: Drug Activation and Drug Resistance Mechanisms, 17 Weber, 1993, Activation of the anti-cancer drug ifosphamide by rat liver microsomal P450 enzymes, Biochem. Pharmacol., 45, 1685, 10.1016/0006-2952(93)90310-S White, 1980, A method utilizing human lymphocytes with in vitro metabolic activation for assessing chemical mutagenicity by SCE analysis, Mutation Res., 69, 283, 10.1016/0027-5107(80)90093-7 Wild, 1978, Cytogenetic effects in the mouse of 17 chemical mutagens and carcinogens evaluated by the micronucleus test, Mutation Res., 56, 319, 10.1016/0027-5107(78)90200-2 Wilmer, 1984, Sister chromatid exchange induction in mouse B- and T- lymphocytes exposed to cyclophosphamide in vitro and in vivo, Cancer Res., 44, 880 Wyrobek, 1975, Chemical induction of sperm abnormalities in mice, 72, 4425 Wyrobek, 1983, An evaluation of the mouse sperm morphology test and other sperm tests in nonhuman mammals: A report of the US Environmental Protection Agency Gene-Tox Program, Mutation Res., 115, 1, 10.1016/0165-1110(83)90014-3 Wyzszynska, 1988, In vivo study on the frequency of sister chromatid exchange (SCE) and micronuclei (MN) induced by cyclophosphamide in bone marrow and spleen cells in rodents, Pol. J. Occup. Med., 1, 322 Xamena, 1991, Additional data in support of the quadruplicated white-ivory reversion system to test for somatic genotoxicity in Drosophila melanogaster, Mutation Res., 252, 305, 10.1016/0165-1161(91)90010-6 Xing, 1992, Transplacental genotoxicity of triethylenemelamine, benzene, and vinblastine in mice, Teratogen. Carcinogen. Mutagen., 12, 223, 10.1002/tcm.1770120505 Yamamoto, 1980, A comparison of diameters of micronuclei induced by clastogens and by spindle poisons, Mutation Res., 71, 127, 10.1016/0027-5107(80)90012-3 Yamamoto, 1981, Studies on micronuclei time response and on the effects of multiple treatments of mutagens on induction of micronuclei, Mutation Res., 90, 163, 10.1016/0165-1218(81)90079-3 Yuan, 1987, Aneuploidy determination in C-banded mouse metaphase II oocytes following cyclophosphamide treatment in vivo, Mutation Res., 179, 209, 10.1016/0027-5107(87)90311-3 Zenick, 1994, Assessment of male reproductive toxicity: A risk assessment approach, 937 Zhurkov, 1978, Dynamics of dominant lethal mutations in male mice exposed for different periods to cyclophosphamide in drinking water, Genetika, 14, 824 Zhurkov, 1982, Effects of long-wave ultraviolet radiation on the frequency of chromosome aberrations induced by cyclophosphamide in mouse bone marrow cells, Tsitol. Genet., 16, 6 Zijlstra, 1988, The ratio of induced recessive lethals to ring-x loss has prognostic value in terms of functionality of chemical mutagens in Drosophila melanogaster, Mutation Res., 201, 27, 10.1016/0027-5107(88)90108-X Adams, 1981, Cyclophosphamide-induced spermatogenic effects detected in the F1 generation by behavioral testing, Science, 211, 80, 10.1126/science.7444453 Boumpas, 1993, Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy, Ann. Intern. Med., 119, 366, 10.7326/0003-4819-119-5-199309010-00003 Chang, 1988, Use of an established human hepatoma cell line with endogenous bioactivation for gene mutation studies, Cell Biol. Toxicol., 4, 267, 10.1007/BF00058736 Ginsberg, 1981, Acrosomal proteolytic assay for detection of mutagens in mammals, Mutation Res., 91, 413, 10.1016/0165-7992(81)90024-5 Hilscher, 1968, Untersuchungen am Samenepithel der Ratte nach Gaben von Endoxan und Natulan, Beitr. Pathol. Anat., 137, 452 Matsuoka, 1979, Chromosomal aberration test on 29 chemicals combined with S9 mix in vitro, Mutation Res., 66, 277, 10.1016/0165-1218(79)90089-2 McDevitt, 1993, Exposure of hospital pharmacists and nurses to antineoplastic agents, J. Occup. Med., 35, 57 Michaelis, 1961, Die Induktion von chromosomenaberrationen durch Mitomen und Endoxan bei Vicia faba und der Transportform-Wirkform-Mechanismus, Biol. Zbl., 80, 301 Ping, 1990, The cofactor effect: variocele and infertility, Fertil. Steril., 54, 143, 10.1016/S0015-0282(16)53651-6 Schleiermacher, 1966, Über den Einfluss von Trenimon und Endoxan auf die Meiose der männlichen Maus: II Cytogenetische befunde nach behandlung mit trenimon und Endoxan, Humangenetik, 3, 134, 10.1007/BF00291295 Schleiermacher, 1970, The activity of alkylating agents, II. Histological and cytogenetic findings in spermatogenesis, 317 Siimes, 1990, Small testicles with impaired production of sperm in adult male survivors of childhood malignancies, Cancer, 1303, 10.1002/1097-0142(19900315)65:6<1303::AID-CNCR2820650608>3.0.CO;2-D Sorsa, 1985, Occupational exposure to anticancer drugs — Potential and real hazards, Mutation Res., 154, 135, 10.1016/0165-1110(85)90024-7 Trasler, 1986, Chronic low dose cyclophosphamide treatment of adult male rats: effect on fertility, pregnancy outcome and progeny, Biol. Reprod., 34, 275, 10.1095/biolreprod34.2.275