Strain differences in the metabolic activation of aflatoxin B₁ in the rat

Abstract

1. It has been reported that female Fischer rats are much more susceptible to the hepatocarcinogenic effects of aflatoxin B₁ than female DA rats.

2. Female Fischer rats are approximately twice as active as female DA rats in producing adducts of aflatoxin B₁ with DNA in vivo, in freshly isolated hepatocytes and with hepatic microsomal fractions.

3. There was no difference between the hepatic microsomal fractions from Fischer and DA rats in the production of adducts between aflatoxin B₁ and microsomal protein.

4. The difference between the strains in the formation of adducts with DNA was not due to either the activity of glutathione S-transferases or to the selective destruction of cytochrome P-450 in the DA strain.

5. None of the differences reported here was of sufficient magnitude to explain the difference in susceptibility of the rat strains to the hepatocarcinogenic effects of aflatoxin B₁.