Induction and modulation of hepatic preneoplasia and neoplasia in the rat by dehydroepiandrosterone.
Dehydroepiandrosterone (DHEA), the main adrenal steroid in humans and a precursor in androgen and estrogen biosynthesis, acts as a peroxisome proliferator and as a hepatocarcinogen in rats. Neoplasms emerge from a glycogenotic/amphophilic/basophilic preneoplastic cell lineage. A higher female tumor incidence suggests a relevant influence of sex hormones. DHEA enhances hepatocarcinogenesis induced by N-nitrosomorpholine (NNM), which is characterized by the glycogenotic/basophilic cell lineage. The tumor promoting effect is related to an additional amphophilic/basophilic preneoplastic lesion sequence and to faster proliferation of the basophilic preneoplastic lesions. Nevertheless, hepatocellular carcinomas provided under DHEA treatment seem to have a less malignant phenotype compared to tumors induced by NNM only. Further, DHEA treatment reduces growth and generation of glycogen storage foci (GSF) in initial NNM-treated rats. Thus, DHEA treatment results in both, a growth stimulation of the late basophilic lesion type with an additional amphophilic lesion sequence, and in a growth inhibition of early preneoplastic lesions, addressing especially GSF. DHEA also inhibits the growth of physiologically proliferating liver tissue. This might be explained by a DHEA related cellular metabolism, which results in significant energy consumption. Additionally, a DHEA-induced alteration of cytokine levels might contribute to this growth inhibition as well.
Mayer
Doris
D
Research Group Hormones and Signal Transduction, Deutsches Krebsforschungszentrum, Heidelberg, Germany. d.mayer@dkfz-heidelberg.de
Forstner
Klaus
K
Kopplow
Kathrin
K
D000818:Animals; D003043:Cocarcinogenesis; D003687:Dehydroepiandrosterone / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D009602:Nitrosamines / Q000633:toxicity; D011230:Precancerous Conditions / Q000139:chemically induced*; D051381:Rats
D009602:Nitrosamines; C002741:N-nitrosomorpholine; D003687:Dehydroepiandrosterone