Comparative cytogenetic analysis of bone marrow damage induced in male B6C3F1 mice by multiple exposures to gaseous 1,3‐butadiene
Tóm tắt
Groups of male B6C3F1 mice (N = 12) were exposed to ambient air or to gaseous 1,3‐butadiene (BD) at 6.25, 62.5, and 625 ppm for 10 exposure days (6 hr + T90/day). Exposure to BD induced in bone marrow: 1) a significant increase in the frequency of chromosomal aberrations (CA); 2) a significant elevation in the frequency of sister chromatid exchanges (SCE); 3) a significant lengthening of the average generation time (AGT); 4) a significant depression in the mitotic index (MI); and, as measured in the peripheral blood, 5) a significant increase in the proportion of circulating polychromatic erythrocytes (%PCE), and 6) a significant increase in the level of micronucleated PCE (MN‐PCE) and micronucleated normochromatic erythrocytes (MN‐NCE). The most sensitive indicator of genotoxic damage was the frequency of SCE (significant at 6.25 ppm), followed by MN‐PCE levels (significant at 62.5 ppm), and then by CA and MN‐NCE frequencies (significant at 625 ppm). The most sensitive measure of cytotoxic damage was AGT (significant at 62.5 ppm), followed by %PCE (significant at 625 ppm), and then by MI (significant by trend test only). Because each cytogenetic endpoint was evaluated in every animal, a correlation analysis was conducted to evaluate the degree of concordance among the various indicators of genotoxic and cytotoxic damage. The extent of concordance ranged from a very good correlation between the induction of MN‐PCE and the induction of SCE (correlation coefficient r = 0.9562) to the lack of a significant correlation between the depression in the MI and any other endpoint (r < 0.37).
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Tài liệu tham khảo
Choy W‐N, 1986, Genotoxicity of 1,3‐butadiene. Induction of bone marrow micronuclei in B6C3F1 mice and Sprague‐Dawley rats in vivo, Environ Mutagen, 8, 18
Cunningham MJ, 1986, Genotoxicity of 1,3‐butadiene. Induction of sister chromatid exchanges in B6C3F1 mice and Sprague‐Dawley rats, Environ Mutagen, 8, 20
Hazleton Laboratories Europe(1981):1 3‐Butadiene. Inhalation Teratogenicity Study in the Rat. Final Report and Addendum No. 2788‐522/3. Hazleton Labs Harrowgate HG3 IPY UK.
Ivett JL, 1982, Average generation time: A new method for analyzing cellular proliferation kinetics based on bromodeoxyuridine‐dependent chromosomal differential staining patterns, Environ Mutagen, 4, 358
Kirk‐Othmen Encyclopedia of Chemical Technology, 1979, Butadiene, 313
Luke CA, 1985, Duration and regimen induced micronuclei in the peripheral blood of mice exposed chronically to benzene, Environ Mutagen, 7, 29
Margolin BH, 1986, Evaluation of Short‐Term Tests for Carcinogens: Report of the International Programme on Chemical Safety's Collaborative Study on In Vivo Assays
ThurmondLM LauerLD HouseRV StillmanWS IronsRD SteinhagenWH DeanJW(1986):Effect of short‐term inhalation exposure to 1 3‐butadiene on murine immune functions. Toxicol Applied Pharmacol (in press).
Tice RR, 1985, Toxicology of the Blood and Bone Marrow, 119
TiceRR LukeCA ShelbyMD(1986):Methyl isocyanate: An evaluation of in vivo cytogenetic activity. Environ Mutagen (in press).