Sister chromatid exchanges induced in rabbit lymphocytes by ethylene oxide after inhalation exposure
Tóm tắt
Ethylene oxide, which is the simplest epoxide and an extremely important commercial compound, has been used by many investigators as a model compound to study mutagenicity by alkylation of DNA. Knowledge of in vivo dose‐effect relations under experimental conditions may provide further insight into the dynamics of the sister chromatid exchange (SCE) response. It may also provide information on temporal aspects of sampling design for human worker populations. Groups of four male New Zealand white rabbits were exposed in inhalation chambers to 0, 10, 50, and 250 parts per million (ppm) ethylene oxide for 6 hr a day, 5 days a week, for 12 weeks. Peripheral blood samples were taken before the start of exposure, at intervals during exposure, and up to 15 weeks after the end of exposure to measure SCE rates in peripheral lymphocytes as well as standard hematological endpoints. Additionally, the level of reduced glutathione (GSH) in liver and blood was measured in a set of concurrently exposed animals at the end of the 12‐week exposure. Results show that exposure to 10 ppm does not cause a detectable increase in SCE rates. However, exposure to 50 and 250 ppm does cause an increase in SCEs that decreases after exposure ends, but still remains above baseline levels 15 weeks after exposure. Hematological and GSH measurements did not differ between control and exposed groups. These results indicate that inhalation exposure to the mutagenic alkylating agent ethylene oxide results in a dose‐related SCE effect, and that SCE is a more sensitive indicator of exposure than either standard hematological end points or GSH levels.
Từ khóa
Tài liệu tham khảo
Altman PL, 1974, Biology Data Book
Beutler E, 1963, Improved method for the determination of blood glutathione, J Lab Clin Med, 61, 882
Consolazio FC, 1963, Physiological Measurements of Multiple Functions in Man, 196
Crossen PE, 1978, Cytogenetic studies of pesticide and herbicide sprayers, N Zealand Med J, 88, 192
Ehrenberg L, 1979, Assessing Chemical Mutagens. The Risk to Humans
Ehrenberg L, 1967, Haematologic studies on persons occupationally exposed to ethylene oxide, Int Atomic Energy Agency Report SM, 92, 327
Embree JW, 1975, Mutagenicity of ethylene oxide, Toxicol Appl Pharmacol, 33, 172
Fjellstedt TA, 1973, Enzymatic conjugation of epoxides with glutathione, J Biol Chem, 248, 3702, 10.1016/S0021-9258(19)43983-5
Melby EC, 1976, Handbook of Laboratory Animal Science
Lambert B, 1978, Sister chromatid exchanges in lymphocyte cultures of patients receiving chemotherapy for malignant disorders, Cancer Treatment Rep, 62, 1413
LeidelNA BuschKA LynchJR(1977):Occupational exposure sampling strategy manual. NIOSH January 1977 DHEW Publ No 77–173.
Nakao Y, 1961, Test of a possible correlation between crosslinking and chromosome breaking abilities of chemical mutagens, Z Vererbungsl, 93, 356
Use of ethylene oxide as a sterilant in medical facilities. DHEW (NIOSH) Publ No 77–200 August 1977.
Weisbroth SH, 1974, The Biology of the Laboratory Rabbit, 57