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
beta-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.