Cigarette smoking is a determinant of DT-diaphorase gene expression in human non-small cell lung carcinoma.
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.
Gasdaska
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Arizona Cancer Center, University of Arizona Health Sciences Center, Tucson 85724.
Powis
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Hyman
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D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015152:Blotting, Northern; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology*; D008175:Lung Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000032:analysis* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D012907:Smoking / Q000378:metabolism*
D012333:RNA, Messenger; D016660:NAD(P)H Dehydrogenase (Quinone)