Study of the endocrine status, which is often disturbed during hepatocarcinogenesis, is particularly valuable because gonadal function and
hormone production regulate hepatic metabolism of the
carcinogen. Sex
steroids can even promote
carcinogenesis. After
aflatoxin B1 induction of liver
carcinogenesis in adult female Sprague Dawley rats, livers were examined by histology, fluorescence microscopy of the
carcinogen and its metabolites, and alphafetoprotein (AFP) assays. Ovarian activity was assessed, and both
progesterone and
estradiol levels were determined. Administration of a diet containing 10.32% total
protein plus 2 ppm
aflatoxin B1 was observed to prevent development of liver
tumors during the 300 day study period. This finding is especially interesting for the study of populations suffering from
malnutrition and exposed to dietary
carcinogens. Under study conditions,
aflatoxin B1 did not cause elevation of AFP levels, as occurs with other hepatotoxic substances. This absence of a rise in AFP despite liver alterations explains the surprising lack of ovarian modifications. In other experiments, AFP has been shown to cause genital function blockade which leads to reduced levels of hormonal promoters, for example during N2 fluorenylacetamide
carcinogenesis. The endocrine reaction implicated in the development of
tumors during
carcinogenesis thus appears closely related to the nature of the
carcinogen, AFP production, and the composition of the diet.