Cytosolic NAD(P)H:(quinone-acceptor)oxidoreductase in human normal and tumor tissue: effects of cigarette smoking and alcohol.
NAD(P)H:(quinone-acceptor)oxidoreductase (QAO), previously known as DT-diaphorase, catalyzes the reduction of quinones to hydroquinones. Enhanced activity of the enzyme has been suggested to protect cells against the cellular toxicity and carcinogenicity of quinones, but may activate some cytotoxic anti-tumor quinones. Cytosolic levels of QAO, carbonyl reductase (CR) and total quinone reductase activity have been measured in normal and tumorous human tissues. QAO was the major component of the total cytosolic quinone reductase activity in all the tissues investigated. CR represented 10 to 28% of the total cytosolic quinone reductase activity in normal tissue. Normal tissue QAO was high in the stomach and kidney, and lower in the lung, liver, colon and breast. Primary tumor from lung, liver, colon and breast had elevated levels of QAO compared to normal tissue, while tumor from kidney and stomach had lower levels. CR was not significantly altered in tumor tissue, except in the case of lung and colon tumor which showed an increase compared to normal tissue. A major determinant of the variability of human lung tumor QAO was the cigarette-smoking history of the donor. Non-smokers and past smokers had high levels of tumor QAO compared to normal tissue. Smokers had levels of tumor QAO that were not significantly different from those of normal tissue QAO. Smokers had a small increase in normal lung QAO compared to non-smokers. Alcohol use was associated with an increase in lung tumor QAO but had no effect on QAO in normal lung. The function of QAO in tumors is not known but the elevated activity of QAO in some tumors and the apparent depressant effect of smoking could influence the response of these tumors to quinone drugs or toxic agents that are metabolized by QAO.
Schlager
J J
JJ
Department of Pharmacology, Mayo Clinic, Rochester, MN 55905.
Powis
G
G
D000428:Alcohol Drinking; D000818:Animals; D003106:Colon / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology*; D006801:Humans; D008168:Lung / Q000201:enzymology; D008175:Lung Neoplasms / Q000201:enzymology; D008297:Male; D009369:Neoplasms / Q000201:enzymology*; D011808:Quinone Reductases / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D012907:Smoking / Q000378:metabolism*
D011808:Quinone Reductases