Application of an immunoassay for cyclic acrolein deoxyguanosine adducts to assess their formation in DNA of Salmonella typhimurium under conditions of mutation induction by acrolein.
Acrolein has been shown to form cyclic deoxyguanosine adducts when it reacts with DNA in vitro. In this study, we have used a recently developed immunoassay for these adducts to study their formation in DNA from Salmonella typhimurium exposed to acrolein. Acrolein--deoxyguanosine adducts were formed in a dose-dependent fashion in Salmonella tester strains TA100 and TA104, reaching levels as high as 5 mumol adduct per mol deoxyguanosine. Using the liquid pre-incubation assay, acrolein-induced mutations were also found in strains TA100 and TA104. The correlation between acrolein--deoxyguanosine adduct concentration and acrolein-induced mutations in TA100, which contains GC base pairs at the site of reversion, suggests that the acrolein--deoxyguanosine adduct is a promutagenic lesion. That mutations are also seen in TA104 which contains AT base pairs at the site of reversion suggest that adducts of bases other than deoxyguanosine may also be important in the mutagenic activity of acrolein.
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Division of Chemical Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, NY 10595.
Akerkar
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Chung
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D000171:Acrolein / Q000633:toxicity*; D000447:Aldehydes / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004269:DNA, Bacterial / Q000187:drug effects*; D003849:Deoxyguanosine; D007118:Immunoassay; D009154:Mutation / Q000187:drug effects*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D000447:Aldehydes; D000911:Antibodies, Monoclonal; D004269:DNA, Bacterial; D000171:Acrolein; D003849:Deoxyguanosine