US EPA

2206527 

Journal Article 

Differences in aflatoxin B1 susceptibility of rat and mouse are correlated with the capability in vitro to inactivate aflatoxin B1 epoxide 

Degen, GH; Neumann H-G 

1981 

Yes 

Carcinogenesis
ISSN: 0143-3334
EISSN: 1460-2180 

HEEP/81/12059 

LOND 

LOND 

299-306 

HEEP COPYRIGHT: BIOL ABS. The metabolism of (14C)aflatoxin B1 (AFB1) (a carcinogen) was studied in liver postmitochondrial supernatants. Livers of untreated and phenobarbital and Aroclor 1254 pretreated male rats, and those of untreated female rats and mice of both sexes were used. Aflatoxin B1 (AFB1), aflatoxin Q1, aflatoxin M1 and aflatoxin P1 accounted for 90% of the extracted radioactivity. The major water-soluble metabolite was the 8,9-dihydro-8-(S-glutathionyl)-9-hydroxy-AFB1 which accounted for 80% of hydrophilic radioactivity in some experiments. Overall metabolic conversion of AFB1 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. Metabolic activation and metabolic inactivation values indicate that mouse liver preparations have a potential for production of AFB1-8,9-epoxide that is similar to that of uninduced or induced rat liver preparations; the mouse liver preparations 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; the fraction of the GSH-conjugate was doubled. If these results were to apply to the in vivo situation, the more efficient inactivation of AFB1-epoxide by conjugation with glutathione could explain the lower susceptibility of mice as compared to rats against AFB1-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.