32P-postlabeling analysis of adducts formed between DNA and safrole 2',3'-epoxide: absence of adduct formation in vivo.
We have used the 32P-postlabeling technique to examine the binding of safrole 2',3'-oxide to DNA. At least 8 covalent adducts are formed when calf thymus DNA is incubated with this oxygenated metabolite of safrole in vitro. However, no corresponding adducts are formed with liver DNA when whole animals are exposed to safrole 2',3'-oxide, or safrole itself. Although safrole 2',3'-oxide is readily formed in vivo, and is sufficiently reactive to covalently bind to DNA, it is probably not a factor in the in vivo genotoxicity of safrole. We also demonstrate that adducts with similar mobility to the major safrole 2',3'-oxide-DNA adduct are formed in vitro between safrole 2',3'-oxide and deoxyguanosine, and also between its chemical analogs allylbenzene 2',3'-oxide or estragole 2',3'-oxide and DNA.
Qato
M K
MK
Department of Pharmacology, University of Illinois College of Medicine at Chicago, 60612.
Guenthner
T M
TM
D000818:Animals; D018736:DNA Adducts / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010761:Phosphorus Radioisotopes; D012451:Safrole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity
D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; C009196:safrole oxide; D012451:Safrole