PMID: 7547240Oct 1, 1995Paper

DT-diaphorase activity in normal and neoplastic human tissues; an indicator for sensitivity to bioreductive agents?

British Journal of Cancer
E Smitskamp-WilmsG J Peters

Abstract

DT-diaphorase (DTD) is an important enzyme for the bioreductive activation of the new alkylating indoloquinone EO9. In preclinical studies, EO9 has shown selective anti-tumour activity against solid tumours and under hypoxic conditions. The levels of three reductive enzymes have been determined in three types of human solid tumours, together with corresponding normal tissues and normal liver. DTD enzyme activities were measured in tumour extracts using 2,6-dichlorophenolindophenol (DCPIP) and NADH as substrates; cytochrome P450 reductase or cytochrome b5 reductase activities were assessed with cytochrome c and NADPH or NADH respectively. DTD activity was highest in non-small-cell lung (NSCLC)-tumours (mean 123 nmol DCPIP min-1 mg-1), followed by colon carcinoma (mean 75 nmol min-1 mg-1) and squamous cell carcinoma of the head and neck (6-fold lower than NSCLC). DTD activity was very low in normal liver and normal lung (4-6 nmol min-1 mg-1), while the levels in normal colon mucosa or normal mucosa of the head and neck region were in the same range as the corresponding tumours. The levels of the two other reductive enzymes, cytochrome P450 reductase (CP450R) and cytochrome b5 reductase (Cb5R), were 5 to 25-fold lower than those o...Continue Reading

Citations

Apr 17, 1999·British Journal of Cancer·J K Kepa, D Ross
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Jan 14, 2004·The Journal of Pharmacology and Experimental Therapeutics·Yusheng HanSu-shu Pan
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Aug 17, 2021·Frontiers in Oncology·Yue LiXiao-Feng Li

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