TEMPORAL PATTERNS OF COVALENT DNA ADDUCTS IN RAT-LIVER AFTER SINGLE AND MULTIPLE DOSES OF AFLATOXIN-B1

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (1) , 197-203
Abstract
Patterns of covalent modifications of DNA produced in rat liver after exposure to single and multiple doses of [the carcinogen] aflatoxin B1 were examined. The principal product, previously identified as 2,3-dihydro-3-hydroxy(N7-guanyl) aflatoxin B1, 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 h. Similar kinetics of disappearance were seen for 2 other aflatoxin adducts, one of which was previously identified as an N7-guanine adduct of aflatoxin P1. The kinetics of formation and disappearance differed for 2 other products believed to be produced by scission of the imidazole ring of the 7-substituted guanine moiety of the principal adduct in the DNA molecule. These adducts were removed slowly, if at all, during the 72 h period studied. Approximately 20% of the principal N7 adduct initially formed was converted to these products in 24 h, at which time they were the predominant lesions in DNA. Administration of multiple doses of aflatoxin B1, 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.