Metabolic activation of aflatoxin B₁ by liver tissue from male Fischer F344 rats of various ages

The effect of aging on the ability of the liver to activate chemical procarcinogens was studied using 12-, 18-, and 27-month-old male Fischer F344 rats. The cytochrome P-450 content of the S9 and microsomal fractions of the liver decreased approximately 30% between 12 and 18 months of age. The structural conformation of cytochrome P-450 in microsomes from 12-, 18-, and 27-month-old rats was studied using electron-spin resonance spectroscopy. An age-related decrease in the amount of cytochrome P-450 ferric iron in the liver microsomes was observed. The conversion of the chemical procarcinogen aflatoxin B₁ to mutagenic compounds by the S9 and microsomal fractions of liver was measured using the Salmonella typhimurium bioassay. A 40-50% decrease in the metabolic activation of the aflatoxin B₁ was observed between 12 and 18 months of age. However, the activation of aflatoxin B₁ did not change after 18 months of age. The age-related decrease in the activation of aflatoxin B₁ by liver appears to be due to a decrease in the metabolic activity of the mixed-function oxidase system.