Cigarette smoking is a determinant of DT-diaphorase gene expression in human non-small cell lung carcinoma

• Published in: Cancer research (Chicago, Ill.) Vol. 53; no. 22; pp. 5458 - 5461
• Main Authors: GASDASKA, P. Y, POWIS, G, HYMAN, P, FISHER, H
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.11.1993
• Subjects: Aged; Aged, 80 and over; Base Sequence; Biological and medical sciences; Blotting, Northern; Carcinoma, Non-Small-Cell Lung - enzymology; Female; Humans; Liver - enzymology; Lung - enzymology; Lung Neoplasms - enzymology; Male; Medical sciences; Middle Aged; Molecular Sequence Data; NAD(P)H Dehydrogenase (Quinone) - analysis; NAD(P)H Dehydrogenase (Quinone) - metabolism; RNA, Messenger - analysis; Smoking - metabolism; Tobacco, tobacco smoking; Toxicology; Human; Respiratory disease; Enzyme; Tobacco smoking; Exploration; Malignant tumor; Gene expression; Bronchopulmonary; Tissue; NADPH dehydrogenase (quinone); Messenger RNA; Oxidoreductases; Non small cell carcinoma
• ISSN: 0008-5472; 1538-7445

The levels of NAD(P)H:(quinone-acceptor) oxidoreductase (EC.1.6.99.2) (DT-diaphorase) mRNA and enzyme activity have been studied in paired human normal lung and non-small cell lung tumor samples from patients with a history of cigarette smoking. There were significantly higher levels of DT-diaphorase mRNA (1.2 kilobases) in lung tumor compared to normal lung tissue of patients who had stopped smoking more than 6 months before surgery, with relative values (normalized to beta-actin mRNA) of 29.6 +/- 7.8 (SE) in the lung tumor compared to 11.7 +/- 2.2 in normal lung tissue (P < 0.05). There was no significant difference in DT-diaphorase mRNA between lung tumor and normal lung tissue of subjects who were smokers at the time of surgery, with values of 16.5 +/- 2.1 and 15.3 +/- 2.5 (P > 0.05), respectively. DT-diaphorase enzyme activity in normal and tumor lung tissue was positively correlated with DT-diaphorase mRNA (r = 0.908, P < 0.01). The results of the study suggest that DT-diaphorase does not function as an inducible protectant enzyme in human lung against oxidant species and carcinogens present in cigarette smoke. Metabolism of some anticancer drugs by DT-diaphorase can alter their activity. Differences in DT-diaphorase between lung tumors of smokers and past smokers might alter the response to these drugs.