Comparative cytogenetic analysis of bone marrow damage induced in male B6C3F1 mice by multiple exposures to gaseous 1,3-butadiene.
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 less than 0.37).
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D002070:Butadienes / Q000633:toxicity*; D002467:Cell Nucleus / Q000648:ultrastructure; D002869:Chromosome Aberrations; D004249:DNA Damage; D004852:Epoxy Compounds / Q000633:toxicity; D004913:Erythrocytes, Abnormal / Q000187:drug effects; D005740:Gases; D008297:Male; D051379:Mice; D008940:Mitotic Index / Q000187:drug effects; D009152:Mutagenicity Tests; D012854:Sister Chromatid Exchange
D002070:Butadienes; D004852:Epoxy Compounds; D005740:Gases; C024370:3,4-epoxy-1-butene; C007366:diepoxybutane