In vivo covalent binding of aflatoxin B 1 and aflatoxin M 1 to liver DNA of rat, mouse and pig

Abstract

[ 14C]Aflatoxin B 1 (AFB 1) was isolated from cultures of Aspergillus parasiticus grown on [1- 14C]sodium acetate. Covalent binding of AFB 1 to liver DNA of rat and mouse was determined 6–8 h after oral administration. The effectiveness of covalent binding, expressed as DNA binding per dose in the units of a ‘Covalent Binding Index’ (CBI), (μmol aflatoxin/mol DNA nucleotides)/(mmol aflatoxin/kg animal), was found to be 10 400 for rats and 240 for mice. These CBI partly explain the different susceptibility of the two species for the incidence of hepatic tumors. The corresponding values for pig liver DNA, 24 and 48 h after oral administration, were found to be as high as 19 100 and 13 300. DNA-binding has not so far been reported for this species although it could represent an appropriate animal model for studies where a human-like gastrointestinal tract physiology is desirable. Aflatoxin M 1 (AFM 1) is a metabolite found in the milk of cows that have been fed AFB 1-contaminated diet. [ 14C]AFM 1 was also found to be produced by cultures of A. parasiticus giving a yield of about 0.3% of the total aflatoxins. A test for covalent binding to rat liver DNA revealed a CBI of 2100 showing that AFM 1 must also be regarded as a strong hepatocarcinogen. It is concluded that AFB 1 contaminations should be avoided in dairy feed.