Regulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible expression of aldehyde dehydrogenase in hepatoma cells.
The environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces the expression of a number of genes. The biochemical process of the induction of aldehyde dehydrogenase (ALDH-3) was investigated in rat H4IIE hepatoma cells in culture. The kinetics of ALDH-3-induction exhibited parallel increases in the rate of transcription, mRNA, protein, and enzyme activity, all reaching a plateau at 36-48 h after addition of TCDD. Half maximal and maximal inductions occurred at 0.1 and 1 nM of TCDD, respectively. No significant changes in the half-life of ALDH-3 mRNA (14 h) were observed in the cells exposed to three different concentrations of TCDD. Other inducers of xenobiotic metabolism, such as 3-methylcholanthrene and beta-naphthoflavone, also induced ALDH-3 mRNA to a similar level as TCDD, whereas antioxidants or electrophiles, such as tert-butylhydroquinone and dimethyl fumarate, did not show any induction of ALDH-3 mRNA. To examine the involvement of the aryl hydrocarbon receptor (Ah receptor) in the induction of ALDH-3, mouse variant cell lines defective in cytochrome P450IA1-induction and a parental wild type cell line (Hepa1c1c7) were studied. ALDH-3 mRNA and the transcription of its gene were detected in TCDD-treated wild type cells, but not in the treated and untreated variant cells. These results demonstrate that TCDD induces transcription of the ALDH-3 gene via its binding to the Ah receptor.
Takimoto
K
K
McArdle Laboratory for Cancer Research, Department of Oncology, Medical School, University of Wisconsin, Madison 53706.
Lindahl
R
R
Pitot
H C
HC
D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D004790:Enzyme Induction; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000444:Aldehyde Dehydrogenase