Comparison of cytogenetic effects of 3,4-epoxy-1-butene and 1,2:3, 4-diepoxybutane in mouse, rat and human lymphocytes following in vitro G0 exposures.
To understand better the species differences in carcinogenicity caused by 1,3-butadiene (BD), we exposed G0 lymphocytes (either splenic or peripheral blood) from rats, mice and humans to 3, 4-epoxy-1-butene (EB) (20 to 931 microM) or 1,2:3,4-diepoxybutane (DEB) (2.5 to 320 uM), two of the suspected active metabolites of BD. Short EB exposures induced little measurable cytogenetic damage in either rat, mouse, or human G0 lymphocytes as measured by either sister chromatid exchange (SCE) or chromosome aberration (CA) analyses. However, DEB was a potent inducer of both SCEs and CAs in G0 splenic and peripheral blood lymphocytes. A comparison of the responses among species showed that the rat and mouse were approximately equisensitive to the cytogenetic damaging effects of DEB, but the situation for the human subjects was more complex. The presence of the GSTT1-1 gene (expressed in the erythrocytes) reduced the relative sensitivity of the lymphocytes to the SCE-inducing effects of DEB. However, additional factors also appear to influence the genotoxic response of humans to DEB. This study is the first direct comparison of the genotoxicity of EB and DEB in the cells from all three species.
Kligerman
A D
AD
Environmental Carcinogenesis Division (MD-68), US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. kligerman.andrew@epa.gov
DeMarini
D M
DM
Doerr
C L
CL
Hanley
N M
NM
Milholland
V S
VS
Tennant
A H
AH
D000818:Animals; D002070:Butadienes / Q000633:toxicity*; D002273:Carcinogens / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002869:Chromosome Aberrations / Q000235:genetics; D004852:Epoxy Compounds / Q000633:toxicity*; D004912:Erythrocytes / Q000201:enzymology; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007399:Interphase / Q000235:genetics*; D008214:Lymphocytes / Q000187:drug effects*; D051379:Mice; D009152:Mutagenicity Tests; D051381:Rats; D012044:Regression Analysis; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000235:genetics
D002070:Butadienes; D002273:Carcinogens; D004852:Epoxy Compounds; C024370:3,4-epoxy-1-butene; C007366:diepoxybutane; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; C031763:1,3-butadiene