Ovarian function during aflatoxin B1-induced hepatocarcinogenesis in the rat.
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.
D015073:2-Acetylaminofluorene; D016604:Aflatoxin B1; D000348:Aflatoxins; D000818:Animals; D001835:Body Weight; D004044:Dietary Proteins / Q000008:administration & dosage; D004958:Estradiol / Q000097:blood; D005260:Female; D005836:Genitalia, Female / Q000503:physiopathology; D006066:Gonads / Q000032:analysis; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D010053:Ovary / Q000502:physiology*; D011374:Progesterone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D000509:alpha-Fetoproteins / Q000378:metabolism
D000348:Aflatoxins; D004044:Dietary Proteins; D000509:alpha-Fetoproteins; D011374:Progesterone; D004958:Estradiol; D015073:2-Acetylaminofluorene; D016604:Aflatoxin B1