Skip Navigation

Publication Detail

Title: Enhanced levels of several mitochondrial mRNA transcripts and mitochondrial superoxide production during ethinyl estradiol-induced hepatocarcinogenesis and after estrogen treatment of HepG2 cells.

Authors: Chen, J; Gokhale, M; Li, Y; Trush, M A; Yager, J D

Published In Carcinogenesis, (1998 Dec)

Abstract: Ethinyl estradiol (EE) is a strong hepatic promoter and weak complete hepatocarcinogen. Among the effects on rat liver caused by chronic exposure to non-hepatotoxic doses of EE is an initial, transient increase in hepatocyte growth followed by a subsequent inhibition (mitosuppression) of basal and/or induced liver growth. To investigate the mechanism of EE-induced mitosuppression, we performed a differential display and identified 10 genes whose expression was increased 2- to 4-fold in EE-induced, mitosuppressed livers (Chen et al., Carcinogenesis, 17, 2783-2786, 1996). We found that one of these clones was homologous to nuclear genome-encoded mitochondrial ATP synthase subunit E. Here, we describe the identification of two additional cDNAs representing transcripts whose levels were elevated during EE-induced mitosuppression as mitochondrial DNA-encoded cytochrome c oxidase subunit III and ATP synthase 6. In addition, we found that EE, estradiol and the estradiol catechol metabolites, 4-OH-estradiol and 2-OH-estradiol, increased the levels of these and other mitochondrial genome-encoded transcripts in human hepatoma HepG2 cells. We also observed that this increase can be blocked by inhibition of cytochrome P450-mediated estrogen metabolism, and that this increase is accompanied by increased mitochondrial superoxide production, which reflects increased respiratory chain activity.

PubMed ID: 9886577 Exiting the NIEHS site

MeSH Terms: Animals; Carcinogens/toxicity*; Catechols/metabolism; Catechols/toxicity; DNA, Complementary/drug effects; DNA, Complementary/genetics; DNA, Complementary/metabolism; DNA, Mitochondrial/drug effects*; DNA, Mitochondrial/genetics; DNA, Mitochondrial/metabolism*; Estradiol/toxicity; Ethinyl Estradiol/toxicity*; Female; Gene Expression Regulation, Neoplastic/drug effects; Gene Expression/drug effects; Humans; Liver Neoplasms, Experimental/chemically induced*; Liver Neoplasms, Experimental/genetics; Liver Neoplasms, Experimental/metabolism*; Mitochondria, Liver/drug effects*; Mitochondria, Liver/genetics; Mitochondria, Liver/metabolism*; Proton-Translocating ATPases/genetics; RNA, Messenger/metabolism*; Rats; Rats, Inbred F344; Superoxides/metabolism*; Tumor Cells, Cultured

Back
to Top