Vol. 61, Issue 2, 320-325, February 2002

Differential Gene Expression of NAD(P)H:Quinone Oxidoreductase and NRH:Quinone Oxidoreductase in Human Hepatocellular and Biliary Tissue

Ahlke Strassburg, Christian P. Strassburg, Michael P. Manns, and Robert H. Tukey

Departments of Chemistry & Biochemistry and Pharmacology, Cancer Center, University of California, San Diego, La Jolla, California (A.S., C.P.S., R.H.T.) and Department of Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Hannover, Germany (M.P.M.)

NAD(P)H:quinone oxidoreductase (NQO1) and dihydronicotinamide riboside:quinone oxidoreductases (NQO2) are cytosolic flavoproteins that catalyze the two-electron reduction of quinones and quinoid compounds to hydroquinones, thereby promoting detoxification and preventing the formation of highly reactive oxygen species, which lead to DNA and cell damage. Two NQO isoforms, designated NQO1 and NQO2, have been cloned and sequenced. To elucidate their role in carcinogenesis, the gene expression of human NQO1 and NQO2 in paired normal and tumor tissue samples was examined. Quantitative triplex reverse transcriptase polymerase chain reaction was employed to analyze NQO1 and NQO2 mRNA expression in normal hepatic and biliary tissue as well as in cholangiocellular carcinomas (CCC), hepatocellular carcinomas (HCC), and focal nodular hyperplasias (FNH). Coexpression of -actin RNA was used as an internal reference standard and linear ranges of transcript amplification were established for each sample. In normal hepatocellular tissue, the two NQO isoforms were differentially regulated, with a higher expression of NQO2 than NQO1. Malignant hepatocellular tissue (HCC), however, displayed up-regulation of NQO1 and down-regulation of NQO2. Regulation of either transcript was not seen in benign hepatocellular tumor tissue (FNH), which indicates a reciprocal control of NQO genes in hepatocarcinogenesis. Normal biliary tissue expressed a significantly higher level of NQO1 transcripts compared with normal liver, whereas biliary NQO2 levels were significantly lower than in hepatocellular tissue. Comparing the levels of expression in normal and malignant biliary tissue (CCC), no significant differences were noted between the expression levels of either transcript. Thus, this study provides evidence for differential hepatic and biliary regulation of both NQO1 and NQO2.