Sex-dependent, tissue-specific opposing effects of dehydroepiandrosterone on initiation and modulation stages of liver and lung carcinogenesis induced by dihydroxy-di-n-propylnitrosamine in F344 rats.
Administration of the hormone dehydroepiandrosterone (DHEA) (0.6% in the diet) during or subsequent to injections of the carcinogen dihydroxy-di-n-propylnitrosamine (DHPN) (2 X 1000 mg/kg body weight, i.p.) brought about alteration in the yield of preneoplastic lesions in liver and lung of both male and female F344 rats. Concomitant treatment with DHEA was associated with decrease in the numbers and size of glutathione S-transferase (GST-P)-positive hepatocellular foci while effecting a significant increase in development of lung lesions, especially in females. Long-term treatment with the hormone subsequent to carcinogen exposure brought about a reduction in numbers of liver foci in both sexes but in males was also associated with the development of large GST-P-negative foci and nodules of amphophilic/tigroid cell character. DHEA itself did not induce any focal lesions in the lungs or livers of either sex. Thus the hormone increased sensitivity to 'initiation' in the lung while decreasing that in the liver and exerted a sex-dependent pronounced modulation of the phenotype of a proportion of hepatocellular lesions.
Moore
M A
MA
Carcinogenesis Research Unit, School of Pathology, University of NSW, Kensington, Australia.
Weber
E
E
Thornton
M
M
Bannasch
P
P
D000818:Animals; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D009602:Nitrosamines; D009928:Organ Specificity; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
D009602:Nitrosamines; D003687:Dehydroepiandrosterone; C012457:diisopropanolnitrosamine; D005954:Glucosephosphate Dehydrogenase; D005982:Glutathione Transferase