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Temporal Patterns of Covalent DNA Adducts in Rat Liver after Single and Multiple Doses of Aflatoxin B₁¹

Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

We examined patterns of covalent modifications of DNA produced in rat liver after exposure to single and multiple doses of aflatoxin B₁. 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 hr. Similar kinetics of disappearance was seen for two 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 two 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-hr period studied. Approximately 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 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.

¹ Financial supported for this work was provided by Grants 5/P01/ES/00597-06 and 5/T32/ES/07020-02 from the N.I.H.

² To whom requests for reprints should be addressed.

Received 6/26/80. Accepted 10/ 3/80.

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