Differences in aflatoxin B₁-susceptibility of rat and mouse are correlated with the capability <i>in vitro</i> to inactivate aflatoxin B₁- epoxide

Abstract

The metabolism of ( 14 C)aflatoxin B 1 (AFB 1 ) was studied in liver postmitochondrial supernatants. Livers of untreated as well as phenobarbital and Aroclor 1254 pretreated male rats, and those of untreated female rats and mice of both sexes were used. Aflatoxin B 1 (AFB 1 ), aflatoxin Q 1 , aflatoxin M 1 and aflatoxin P 1 were identified and determined in lipophilic extracts by t.l.c. and h.p.l.c. These compounds accounted for more than 90% of the extracted radioactivity. The major watersoluble metabolite was the 8, 9-dihydro-8-(S-glutathionyl)-9-hydroxy-AFB 1 which accounted for more than 80% of hydrophilic radioactivity in some experiments. Overall metabolic conversion of AFB 1 in liver preparations was higher in mice than in untreated rats. Sex differences were not observed in mice but were apparent in rats, with females having the lower metabolic activity. For the purpose of comparison, values for metabolic activation and metabolic inactivation have been estimated. They indicate that mouse liver preparations have a potential for production of AFB 1 -8,9-epoxide that is similar to that of uninduced or induced rat liver preparations; the mouse liver preparations, however, are 2, or 4, times more active in conjugating the epoxide with glutathione than those of untreated male or female rats, respectively. Pretreatment of rats with phenobarbital or Aroclor increased the overall rate of metabolism, but not the fraction of epoxide formed, whereas the fraction of the GSH-conjugate was doubled. If these results were to apply to the in vivo situation, the more efficient inactivation of AFB 1 -epoxide by conjugation with glutathione could explain the lower susceptibility of mice as compared to rats against AFB 1 toxicity, the lower susceptibility of female as compared to male rats, and the decrease of toxicity in rats by phenobarbital pretreatment. It could also contribute towards an understanding of species differences in tumor susceptibility.