Temporal Patterns of Covalent DMA Adducts in Rat Liver after Single and Multiple Doses of Aflatoxin B,'

We examined patterns of covalent modifications of DNA produced in rat liver after exposure to single and multiple doses of aflatoxin Bt. The principal product, previously identified as 2,3-dihydro-3-hydroxy(A/7-guanyl) aflatoxin B,, was removed rapidly from liver DNA in vivo after a 0.6-mg/kg dose was administered i.p. to male Fischer rats. This lesion had an apparent half-life of 7.5 hr. Similar kinetics of disappearance was seen for two other aflatoxin adducts, one of which was previously identified as an A/7-guanine adduci of aflatoxin P,. The kinetics of formation and disappearance differed for two other products believed to be produced by scission of the imidazole ring of the /-substituted guanine moiety of the prin cipal adduct in the DNA molecule. These adducts were re moved slowly, if at all, during the 72-hr period studied. Ap proximately 20% of the principal N7 adduct initially formed was converted to these products in 24 hr, at which time they were the predominant lesions in DNA. Administration of multiple doses of aflatoxin Bi, using a regimen shown to produce a high incidence of hepatocellular carcinoma, caused accumulation of these persistent products in liver DNA over a 14-day period.