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

Jinqiang Chen, Mamata Gokhale, Yunbo Li, Michael A. Trush, James D Yager

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)2187-2193
Number of pages7
JournalCarcinogenesis
Volume19
Issue number12
DOIs
StatePublished - 1998

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Ethinyl Estradiol
Hep G2 Cells
Superoxides
Estrogens
Estradiol
Liver
Mitochondrial Proton-Translocating ATPases
Mitochondrial Genome
Electron Transport Complex IV
Growth
Electron Transport
Mitochondrial DNA
Cytochrome P-450 Enzyme System
mitochondrial messenger RNA
Hepatocytes
Hepatocellular Carcinoma
Complementary DNA
Clone Cells
Genome
Gene Expression

ASJC Scopus subject areas

  • Cancer Research

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Enhanced levels of several mitochondrial mRNA transcripts and mitochondrial superoxide production during ethinyl estradiol-induced hepatocarcinogenesis and after estrogen treatment of HepG2 cells. / Chen, Jinqiang; Gokhale, Mamata; Li, Yunbo; Trush, Michael A.; Yager, James D.

In: Carcinogenesis, Vol. 19, No. 12, 1998, p. 2187-2193.

Research output: Contribution to journalArticle

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