Effects of sex difference and dietary protein level on the binding of aflatoxin B1 to rat liver chromatin proteins in vivo.

The risk of aflatoxin-induced hepatocarcinoma is greater in males than in females and is similarly higher in animals fed 20% casein diets than in those fed 5%. In this study, groups of male and female F344 rats were fed either a 5 or 20% casein diet for 6 weeks. Two hr after a 1-mg/kg i.p. dose of [3H]aflatoxin B1, animals were killed and four protein fractions were sequentially extracted from the liver chromatin of each. Within each treatment group, aflatoxin binding to nonhistones was greater than to histones, both before and after dialysis. Comparing treatments, the higher-risk factors were associated with a greater liver content of aflatoxin as well as with increased binding of both nondialyzable and dialyzable aflatoxin to the various fractions. The high degree of correlation between total liver content and adduct formation implicates the former as a major determinant of the latter. Also associated with the higher-risk factors was a shift in the distribution of dialyzable aflatoxin toward greater adduct formation with one of the nonhistone fractions, suggesting the possibility of a role for noncovalent aflatoxin:protein adducts in hepatocarcinogenesis.