Abstract |
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.
|
Authors | P Y Gasdaska, G Powis, P Hyman, H Fisher |
Journal | Cancer research
(Cancer Res)
Vol. 53
Issue 22
Pg. 5458-61
(Nov 15 1993)
ISSN: 0008-5472 [Print] United States |
PMID | 8221686
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- RNA, Messenger
- NAD(P)H Dehydrogenase (Quinone)
|
Topics |
- Aged
- Aged, 80 and over
- Base Sequence
- Blotting, Northern
- Carcinoma, Non-Small-Cell Lung
(enzymology)
- Female
- Humans
- Liver
(enzymology)
- Lung
(enzymology)
- Lung Neoplasms
(enzymology)
- Male
- Middle Aged
- Molecular Sequence Data
- NAD(P)H Dehydrogenase (Quinone)
(analysis, metabolism)
- RNA, Messenger
(analysis)
- Smoking
(metabolism)
|