Multistage carcinogenesis: implications for risk estimation

Cancer and Metastasis Reviews - Tập 7 - Trang 5-18 - 1988
Hiroshi Yamasaki1
1Programme of Multistage Carcinogenesis, International Agency for Research on Cancer, Lyon Cedex 08, France

Tóm tắt

In undertaking a quantitative estimation of carcinogenesis risk, it is essential to keep in mind that carcinogenesis is a multistage process, and that each stage can be affected by different classes of risk factors. Furthermore, different mechanisms are involved in the various stages of carcinogenesis. Thus, a dose-response analysis of one given factor cannot provide an accurate estimation of carcinogenic risk. Carcinogenic risk estimation is usually undertaken for a specific chemical or group of chemicals; however, the concept of multistage carcinogenesis is based on biological processes and not on the mechanisms of action of the agents involved. It is therefore important to consider three related, but different, factors involved in carcinogenesis: stage, agent, and activity of agent. This is especially important in developing a short-term test for stage-related risk factors, such as tumor-promoting agents. For this reason, carcinogens should not be classified according to only one chemical activity. This article briefly reviews the cellular and molecular mechanisms involved in multistage carcinogenesis, and discusses their implications for risk estimation. Special consideration is given to the effect of treatment frequency on the response of tumor-promoting agents, as seen in long-term tests in experimental animals. It is proposed that exposure frequency be taken into account together with exposure dose.

Tài liệu tham khảo

Foulds L: Neoplastic Development. Academic Press, New York, Vol 1, 1969 Doll R: An epidemiological perspective of the biology of cancer. Cancer Res 38: 3573–3583, 1973 Berenblum I (1975): Sequential aspects of chemical carcinogenesis: skin. In: Becker FF (ed) Cancer: A Comprehensive Treatise, Vol. 1. Plenum Press, New York, 1975, pp 323–344 Boutwell RK: Some biological aspects of skin carcinogenesis. Prog Exp Tumor Res 4: 207–250, 1964 Hecker E: Phorbol esters from croton oil-chemical nature and biological activities. Naturwissenschaften 54: 282–284, 1967 Yamasaki H, Weinstein IB: Cellular and molecular mechanisms of tumor promotion and their implication for risk assessment. In: Vouk VB, Hoel GC, Peakall DB (eds) Methods for Estimating Risk of Chemical Injury: Human and Non-Human Biota and Ecosystems. John Wiley, New York, 1985, pp 155–180 Slaga TJ: Cellular and molecular mechanisms of tumor promotion. Cancer Surveys 2: 595–612, 1983 Farber E, Cameron R: The sequential analysis of cancer development. Adv Cancer Res 31: 125–226, 1980 Weinstein IB, Yamasaki H, Wigler M, Lee LS, Fisher PB, Jeffrey AM, Grunberger D: Molecular and cellular events associated with the action of initiating carcinogens and tumor promoters. In: Griffin AC, Shaw CR (eds) Carcinogens-Identification and Mechanisms of Action. Raven Press, New York, 1979, pp 399–418 Barbacid M: Oncogenes and human cancer: cause or consequence? Carcinogenesis 7: 1037–1042, 1986 Schmahl D: Critical remarks on the validity of promoting effects in human carcinogenesis. J Cancer Res Clin Oncol 109: 260–262, 1985 Matsunaga E: Hereditary retinoblastoma: host factors and age at onset. J Natl Cancer Inst 63: 933–939, 1979 Day NE: Epidemiological evidence of promoting effects: the example of breast cancer. In: Hecker E, Fusenig NE, Kunz W, Marks F, Thielmann HW (eds) Carcinogenesis—A Comprehensive Survey, Vol 7, Cocarcinogenesis and Biological Effects of Tumor Promoters. Raven Press, New York, pp 183–199, 1982 Iversen OH, Astrup EG: The paradigm of two-stage carcinogenesis. A critical attitude. Cancer Invest 2: 51–60, 1984 Schulte-Hermann R: Tumor promotion in the liver. Arch Toxicol 57: 147–158, 1985 Druckrey H: Specific carcinogenic and teratogenic effects of ‘indirect’ alkylating methyl and ethyl compounds, and their dependency on stages of ontogenetic developments. Xenobiotica 3: 271–303, 1973 Ehrenberg L, Brookes P, Druckrey H, Lagerlof B, Litwin J, Williams G: The relation of cancer induction and genetic damage. In: Ramel C (ed) Evaluation of Genetic Risks of Environmental Chemicals, Stockholm, Royal Swedish Academy of Sciences, 1973 Weisburger JH, Williams GM: Carcinogen testing: current problems and new approaches. Science 214: 401–407, 1981 Ivanovic V, Weinstein IB: Glucocorticoids and benzo(a) pyrene have opposing effects on EGF receptor binding. Nature 293: 404–406, 1981 Ivanovic V, Weinstein IB: Benzo(a)pyrene and other inducers of cytochrome P1–450 inhibit binding of epidermal growth factor to cell surface receptors. Carcinogenesis 3: 505–510, 1982 Slaga TJ, Sivak A, Boutwell RK: Mechanism of Tumor Promotion and Cocarcinogenesis. Raven Press, New York, 1978 Hecker E, Fusenig NE, Kunz W, Marks F, Thielmann HW: Cocarcinogenesis and Biological Effects of Tumor Promoters. Raven Press, New York, 1982 Borzsonyi M, Lapis K, Day NE, Yamasaki H (eds) Models, Mechanisms and Etiology of Tumor Promotion. (IARC Scientific Publications No. 56). International Agency for Research on Cancer, Lyon, 1984 Slaga TJ, Butterworth BE: Non-genotoxic Mechanisms in Carcinogenesis. CSH Press, Cold Spring Harbor, N.Y., 1987 (in press) Zarble H, Sukumar S, Arthur AV, Martin-Zanca D, Barbacid M: Direct mutagenesis of H-ras-1 oncogenes by nitroso-methyl-urca during initiation of mammary carcinogenesis in rats. Nature 315: 382–385, 1985 Abbott PJ, Saffhill R: DNA synthesis with methylated poly (dC-dG) templates: evidence for a competitive nature to miscoding by 06-methylguanine. Biochim Biophys Acta 562: 51–61, 1979 Dipple A, Pigott M, Moschel RC, Costantino N: Evidence that binding of 7,12-dimethylbenz(a)anthracene to DNA in mouse embryo cell cultures results in extensive substitution of both adenine and guanine residues. Cancer Res 43: 4132–4135, 1983 Balmain A, Pragnell IB: Mouse skin carcinomas induced in vivo by chemical carcinogens having a transforming Harvey-ras oncogene. Nature 303: 72–74, 1983 Balmain A, Ramsden M, Bowden GT, Smith J: Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas. Nature 307: 658–660, 1984 Quintanilla M, Brown K, Ramsden M, Balmain A: Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature 322: 78–80, 1986 Brown K, Quintanilla M, Ramsden M, Kerr IB, Young S, Balmain A: V-ras genes from Harvey and BALB murine sarcoma viruses can act as initiators of two-stage mouse skin carcinogenesis. Cell 46: 447–456, 1986 Bizub D, Wood AW, Skalka AM: Mutagenesis of the Ha-ras oncogene in mouse skin tumors induced by polycyclic aromatic hydrocarbons. Proc Natl Acad Sci USA 83: 6048–6052, 1986 Yamasaki H, Hollstein M, Martel N, Cabral JRP, Galendo D, Tomatis L: Transplacental induction of a specific mutation in fetal Ha-ras and its critical role in post-natal carcinogenesis. Int J Cancer 40: 818–822, 1987 Wiseman RW, Stowers SJ, Miller EC, Anderson MW, Miller JA: Activating mutations of the c-Ha-ras protooncogene in chemically-induced hepatomas of the male B6C3 F1 mouse. Proc Natl Acad Sci USA 83: 5825–5829, 1986 Hsiao WLW, Gattoni-Celli S, Weinstein IB: Oneogene-induced transformation of C3H 10T1/2 cells is enhanced by tumor promoters. Science 226: 552–555, 1984 Hsiao WLW, Wu T, Weinstein IB: Oncogene-induced transformation of a rat embryo fibroblast cell line is enhanced by tumor promoters. Mol Cell Biol 6: 1943–1950, 1986 Dotto GP, Parada LF, Weinberg RA: Specific growth response of ras-transformed embryo fibroblasts to tumor promoters. Nature 318: 472–475, 1985 Yamasaki H: Modulation of cell differentiation by tumor promoters. In: Slaga TJ (ed) Mechanisms in Tumor Promotion, Vol IV, Cellular Responses to Tumor Promotion. CRC Press, Boca Raton, FL, pp 1–26, 1984 Yuspa SH, Morgan DL: Mouse skin cells resistant to terminal differentiation associated with initiation of carcinogenesis. Nature 283: 72–74, 1981 Nishizuka Y: The role of protein kinase C in cell surface signals transduction and tumor promotion. Nature 306: 693–698, 1984 Trosko JE, Yotti LP, Warren ST, Tsushimoto G, Chang CC: Inhibition of cell-cell communication by tumor promoters. In: Hecker E, Fusenig NE, Kunz W, Marks F, Thielmann HW (eds) Carcinogenesis—A Comprehensive Survey, Vol 7, Cocarcinogenesis and Biological Effects of Tumor Promoters. Raven Press, New York, 1982, pp 565–585 Yamasaki H, Enomoto T: Role of intercellular communication in BALB/c 3T3 cell transformation. In: Barrett JC, Tennant RW (eds) Carcinogenesis—A Comprehensive Survey, Vol. 9, Mammalian Cell Transformation: Mechanisms of Carcinogenesis and Assays for Carcinogens. Raven Press, New York, 1985, pp 179–194 Murray AW, Fitzgerald DJ: Tumor promoters inhibit metabolic cooperation in coculture of epidermal and 3T3 cells. Biochem Biophys Res Commun 91: 395–401, 1979 Loewenstein WR: Junctional intercellular communication and the control of growth. Biochim Biophys Acta 560: 1–65, 1970 Yamasaki H: Tumor promotion: from the viewpoint of cell society. In: Proceedings of the meeting on ‘Theories of Carcinogenesis’, Oslo, 1987 (in press) Yamasaki H: Cellular mechanisms of in vitro cell transformation: role of blocked intercellular communication. In: Ramel C, Lambert B, Magnusson J (eds) Genetic Toxicology of Environmental Chemicals, Part A, Basic Principles and Mechanisms of Action. Alan R. Liss, New York, 1986, pp 285–204 Emerit I, Corutti PA: Tumor promoter phorbol 12-myristate 13-acetate induees a clastogenic factor in human lymphocytes. Proc Natl Acad Sci USA 79: 7509–7513, 1982 Varshavsky A: Phorbol ester dramatically increases incidence of methotrexate-resistant mouse cell: possible mechanisms and relevance to tumor promotion. Cell 25: 561–572, 1981 Parry JM, Parry EM, Barrett JC: Tumor promoters induce mitotic aneuploidy in yeast. Nature 294: 263–265, 1981 Yamasaki H: Tumor promotion-mechanisms and implication to risk estimation. Acta Pharmacol Toxicol 55: 89–106, 1984 Burns F, Albert R, Altshuler B, Morris E: Approach to risk assessment for genotoxic earcinogens based on data from the mouse skin initiation-promotion model. Environ Health Perspect 50: 309–320, 1983 Hill CK, Elkind MM, Han A: Role of repair processes in neoplastic transformation induced by ionizing radiation in C3H10T1/2 cells. In: Barrett JC, Tennant RW (eds) Carcinogenesis, a Comprehensive Survey, Vol 9, Mammalian Cell Transformation. Mechanisms of Carcinogenesis and Assays for Carcinogens. Raven Press, New York, pp 379–397, 1985 Van Duuren BL, Sivak A, Segal A, Seidman I, Katz C: Dose-response studies with a pure tumor-promoting agent, phorbol myristate acetate. Cancer Res 33: 2166–2172, 1973 Verma AK, Boutwell RK: Effects of dose and duration of treatment with the tumor-promoting agent, 12–0-tetradecanoylphorbol-13-acetate on mouse skin carcinogenesis. Carcinogenesis 1: 271–276, 1980 Little JB, Kennedy AR: Promotion of X-ray transformation in vitro. In: Hecker E, Fusenig NE, Kunz W, Marks F, Thielmann HW (eds) Careinogenesis — a Comprehensive Survey, Vol 7, Cocarcinogenesis and Biological Effects of Tumor Promoters. Raven Press, New York, 1982, pp 243–257 Goldsworthy T, Campbell HA, Pitot HC: The natural history and dose-response characteristics of enzyme-altered foci in rat liver following phenobarbital and diethylnitrosamine administration. Carcinogenesis 5: 67–71, 1984 Pitot HC, Goldsworthy TL, Moran S, Kennan W, Glauert HP, Maronpot RR, Campbell HA: A method to quantitate the relative initiating and promoting potencies of hepatoeareinogenic agents in their dose-response relationships to altered hepatic foci. Carcinogenesis 8: 1491–1499, 1987 Williams GM: Epigenetic prometing effects of butylated hydroxyonisole. Fd Chem Toxic 24: 1163–1166, 1986 Pitot HC, Goldworthy T, Moran S, Sirica A, Weeks J: Properties of incomplete earcinogens and promoters in hepatocarcinogenesis. In: Hecker E, Fusenig NE, Kunz W, Marks F, Thielmann HW (eds) Carcinogenesis —a Comprehensive Survey, Vol 7, Cocarcinogenesis and Biological Effects of Tumor Promoters. Raven Press, New York, 1982, pp 85–98 Trosko JE, Dawson B, Yotti LP, Chang CC: Saccharin may act as a tumour promoter by inhibiting metabolic cooperation between cells. Nature 285: 109–110, 1980 Umeda M, Noda K, Ono T: Inhibition of metabolic cooperation in Chinese hamster cells by various compounds including tumour promoters. Gann 71: 614–620, 1980 Noda K, Umeda M, Ono T: Effects of various chemicals including bile acids and chemical carcinogens on the inhibition of metabolic cooperation. Gann 72: 772–776, 1981 Williams GM, Telang S, Tong C: Inhibition of intercellular communication between liver cells by the liver tumour promoter 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane. Cancer Lett 11: 339–344, 1981 Tsushimoto G, Tresko JE, Chang CC, Aust SD: Inhibition of metabolic cooperation in Chinese hamster V79 cells in culture by various polybrominated biphenyl (PBB) congeners. Carcinogenesis 3: 181–185, 1982 Tsushimoto G, Trosko JE, Chang CC, Matsumura F: Inhibition of intereellular communication by chlordecone (kepone) and mirex in Chinese hamster V79 cells in vitro. Toxicol Appl Pharmacol 64: 550–556, 1982 Jone CM, Trosko JE, Chang C, Fujiki H, Sugimura T: Inhibition of intercellular communication in Chinese hamster V79 cells by teleoeidin. Gann 73: 874–878, 1982 Malcolm AR, Millis LJ: Inhibition of metabolic cooperation between Chinese hamster V79 cells by tumor promoters and other chemicals. Ann N Y Acad Sci 407: 448–450, 1983 Aylsworth CF, Jone C, Trosko JE, Meites J, Welsch CW: Promotion of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis by high dietary fat in the rat: possible role of intercellular communication. J Natl Cancer Inst 72: 637–645, 1984 Chen TH, Kavanagh TD, Chang CC, Trosko JE: Inhibition of metabolic cooperation in Chinese hamster V79 cells by various organic solvents and simple compounds. Cell Biol Toxiol 1: 155–171, 1984 Warngard L, Flodstrom S, Ljungquist S, Ahlborg UG: Inhibition of metabolic cooperation in Chinese hamster lung fibroblast cells (V79) in culture by various DDT-analogs. Arch Environ Contam Toxicol 14: 541–546, 1985 Zeilmaker M, Yamasaki H: Inhibition of junctional intercellular communication as a possible short-term test to detect tumor promoting agents: results with nine chemicals tested by dye transfer assay in Chinese hamster V79 cells. Cancer Res 46: 6180–6186, 1986 Enomoto T, Martel Y, Kanno Y, Yamasaki H: Inhibition of cell-cell communication between BALB/c 3T3 cells by tumor promoters and protection by cAMP. J Cell Physiol 121: 323–333, 1984 Mondal S, Heidelberger C: Transformation of C3H-10 1/2 C18 mouse embryo fibroblasts by ultraviolet irradiation and a phorbol ester. Nature 260: 710–711, 1976 Lasne C, Gentil A, Chouroulinkov I: Two-stage malignant transformation of rat fibroblasts in tissue culture. Nature 247: 490–491, 1974 Poiley JA, Raineri R, Pienta RJ: Two-stage malignant transformation in hamster embryo cells. Br J Cancer 39: 8–14, 1979 Hirakawa T, Kakunaga T, Fujiki H, Sugimura T: A new tumor-promoting agent, dihydroteleocidin B, markedly enhances chemically induced malignant cell transformation. Science 216: 527–529, 1982 Rivedal E, Sanner T: Promotional effect of different phorbol esters on morphological transformation of hamster embryo cells. Cancer Lett 17: 1–8, 1982 Enomoto T, Yamasaki H: Phorbol ester-mediated inhibition of intercellular communication in BALB/c 3T3 cells: relationship to enhancement of cell transformation. Cancer Res 45: 2681–2688, 1985 Bannasch P, Griesemer RA, Anders F, Becker R, Cabral JR, Della Porta G, Feron VI, Henschler D, Ito N, Kroes R, Magee PN, Montesano R, Napalkov NP, Nesnow S, Rao GN, Wilbourn J: Early preneoplastic lesions. In: Montesano R, Bartsch H, Vainio H, Wilbourn JD, Yamasaki H (eds) Long-term and Short-term Assays for Carcinogens. A Critical Appraisal (IARC Scientific Publications No. 83). International Agency for Research on Cancer, Lyon, 1986, pp 85–101 Bannasch P, Griesemer RA, Anders F, Becker R, Cabral JR, Della Porta G, Feron VJ, Henschler D, Ito N, Kroes R, Magee PN, McKnight B, Montesano R, Napalkov NP, Nesnow S, Roberfroid M, Slaga TJ, Turusov VS, Wilbourn J, Williams GM: Assays for initiating and promoting activities. In: Montesano R, Bartsch H, Vainio H, Wilbourn JD, Yamasaki H (eds) Long-term and Short-term Assays for Carcinogens. A Critical Appraisal (IARC Scientific Publications No. 83). International Ageney for Research on Cancer, Lyon, 1986, pp 103–126 Peto R: Epidemiology, multistage models and short-term mutagenicity tests. In: Hiatt HH, Watson JD, Winsten JA (eds) Origins of Human Cancer, Vol IV. CSH Press, Cold Spring Harbor, NY, 1977, pp 1403–1428 Weber J, Hecker E: Cocarcinogens of the diterpene estertype from Croton flavens L. and esophageal caneer in Curacao. Experientia 34: 679–682, 1978 Cheng SJ, Sala M, Li MH, Chouroulinkov I: Esophageal cancer in Linxian County, China: a possible etiology and mechanism (initiation and promotion). In: Hecker E, Gusenig NE, Kunz W, Marks F, Thielmann HW (eds) Carcinogenesis —a Comprehensive Survey. Vol 7, Cocarcinogenesis and Biological Effects of Tumor Promoters. Raven Press, New York 1982, pp 167–174 Ito Y, Hirayama T: A new view of the etiology of nasopharyngeal carcinoma. Prev Med 10: 614–622, 1981 Dalldorf G, Linsell CA, Barnhart FE, Martyn R: An epidemiologic approach to the lymphomas of African children and Burkitt's sarcoma of the jaws. Perspect Biol Med 7: 435–449, 1964 Jick H, Watkins RN, Dinan BJ, Madsen S, Rothman KJ, Walker AM: Replacement estrogens and endometrial cancer. New Engl J Med 300: 218–222, 1979 Reddy BS, Weisburger JH, Wynder EL: Colon cancer: bile salts as tumor promoters. In: Slaga TJ, Sivak A, Boutwell RK (eds) Carcinogenesis, Vol 2, Mechanisms of Tumor Promotion and Cocarcinogenesis. Raven Press, New York, 1978, pp 453–464 Greenebaum E, Weinstein IB: Relevance of the concept of tumor promotion to the causation of human cancer. In: Ferroglio CM, Woif M (eds) Progress in Surgical Pathology. Masson Publ, New York, 1981, pp 27–43 Akazaki K: Comparative histological studies on the latent carcinoma of the prostate under different environmental circumstances. In: Doil R, Vodopija I (eds) Host Environmental Interaction in the Etiology of Cancer in Man (IARC Scientific Publications No. 7). International Agency for Research on Cancer, Lyon, 1973, pp 89–97 Linsell CA, Peers FG: Field studies on liver cell cancer. In: Hiatt HH, Watson JD, Winsten JA (eds) The Origins of Human Cancer, Vol IV. CSH Press, Cold Spring Harbor, N.Y., 1977, pp 549–556 Selikoff IJ, Hammond EC: Asbestos and smoking (Editorial). J Am Med Assoc 242: 458–459, 1979 Tuyns AJ: Epidemiology of alcohol and cancer. Cancer Res 39: 2840–2844, 1979