N7-guanine adducts of the epoxy metabolites of 1,3-butadiene in mice lung.
Epoxy metabolites of 1,3-butadiene are electrophilic and can bind to nucleophilic sites in DNA forming DNA adducts. In this study, guanine N7 adducts of epoxy butene and guanine N7 adducts of epoxy butanediol were measured in lung tissues of mice inhalation exposed to various concentrations of 1,3-butadiene. 32P-postlabeling of DNA adducts were used to demonstrate that the DNA adducts derived from epoxybutene and epoxybutanediol were formed in a dose dependent manner. More than 98% of all adducts detected were formed from epoxybutanediol. Enantiomeric distribution of the adducts formed in vivo differs from that of in vitro experiments demonstrated before. In the case of epoxybutene most of the adducts were formed to the terminal carbon of the S-epoxybutene enantiomer. Most of the adducts derived from epoxybutanediol were formed from the 2S-3R enantiomer. The data demonstrates that enzymatic processes involved with activation and/or detoxification of the metabolites are enantiospecific and/or DNA repair machinery repairs the damage with stereochemical considerations. These are the crucial factors if interspecies differences in tumor sensitiveness is concerned.
Koivisto
P
P
Finnish Institute of Occupational Health, The Chemistry Laboratory, Topeliuksenkatu 41 aA, FIN-00250 Helsinki, Finland.
Peltonen
K
K
D000280:Administration, Inhalation; D000818:Animals; D002070:Butadienes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism*; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism; D006018:Glycols / Q000737:chemistry / Q000378:metabolism; D006147:Guanine / Q000737:chemistry; D008168:Lung / Q000378:metabolism*; D051379:Mice; D013237:Stereoisomerism
D002070:Butadienes; D018736:DNA Adducts; D004852:Epoxy Compounds; D006018:Glycols; C080053:3,4-epoxybutane-1,2-diol; D006147:Guanine; C031763:1,3-butadiene