Jornal de Citologia e Histologia

NAD(P)H:Quinone Oxidoreductase 1 Expression in Human Reproductive System and Mitomycin-C Cytotoxicity: A New Chapter for Old Compounds?

Abstract

Francesco Zappa, Timothy Ward, Ennio Pedrinis, John Butler and Alan McGown

NAD(P)H:quinone oxidoreductase 1 (NQO1; DT-diaphorase; DTD) is a cytosolic two-electron reductase, and compounds of the family of quinones such as mitomycin C are efficiently bio-activated by this enzyme. The observation that DT-diaphorase is over-expressed in many cancerous tissues compared to normal tissues has provided us with a selective target that can be exploited in the design of novel anticancer agents. Because information about the cell-specific expression of DT-diaphorase was so scarce, this study was initiated to map the distribution of this enzyme in human tissues. We report here our findings concerning the reproductive organs. Tissue samples taken from various components of the human reproductive system were analysed for expression of DT-diaphorase by immunohistochemistry. We found a strong expression of this enzyme in testicular stromal cells (Leydig’s cells) and in the epithelium of the epididymis and Fallopian tube. These results suggest that quinones bio-activated by DT-diaphorase may be toxic to the reproductive system and cause clinical problems due to testosterone deficiency in men and infertility in both sexes. The implications of these observations need to be considered in pre-clinical evaluation of new anticancer quinones and in patients treated with these compounds.