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Cigarette Smoking Is a Determinant of DT-Diaphorase Gene Expression in Human Non-Small Cell Lung Carcinoma¹

Arizona Cancer Center, University of Arizona Health Sciences Center, Tucson, Arizona 85724

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 ß-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.

¹ Supported by NIH Grant CA 42286. P. H. is a Research Fellow of the Cancer Research Foundation of America.

² To whom requests for reprints should be addressed, at Arizona Cancer Center, 1515 N. Campbell Avenue, Tucson, AZ 85724.

Received 3/15/93. Accepted 9/15/93.