Effect of sex difference on the in vitro and in vivo metabolism of aflatoxin B1 by the rat.

Hepatic microsome-catalyzed metabolism of aflatoxin B1 (AFB1) to aflatoxin M1 and aflatoxin Q1 and the "metabolic activation" of AFB1 to DNA-alylating metabolite(s) were studied in normal male and female Sprague-Dawley rats, in gonadectomized animals, and in castrated males and normal females treated with testosterone. Microsomes from male animals formed 2 to 5 times more aflatoxin M1, aflatoxin Q1, and DNA-alkylating metabolite(s) than those from females. Castration reduced the metabolism of AFB1 by the microsomes from males by about 50%, whereas ovariectomy had no significant effect on AFB1 metabolism by the microsomes from females. Testosterone treatment (4 mg/rat, 3 times/week for about 6 weeks) of castrated immature males and immature females enhanced the metabolism of AFB1 by their microsomes. A sex difference in the metabolism of AFB1 by liver microsomes was also seen in other strains of rats tested: Wistar, Long-Evans, and Fischer. The activity of kidney microsomes for metabolic activation was 1 to 4% that of the liver activity and was generally lower in microsomes from male rats as compared to those from female rats of Sprague-Dawley, Wistar, and Long-Evans strains. The in vitro results obtained with hepatic microsomes correlated well with the in vivo metabolism of AFB1, in that more AFB1 became bound in vivo to hepatic DNA isolated from male rats and from a female rat treated with testosterone than that isolated from control female rats. These data suggest that the differences in hepatic AFB1 metabolism may be the underlying cause of the sex difference in toxicity and carcinogenicity of AFB1 observed in rats.