Overexpression of NAD(P)H:quinone oxidoreductase 1 in human reproductive system

Abstract

NAD(P)H:quinone oxidoreductase 1 (NQO1; DT-diaphorase; DTD) is a two-electron reductase that efficiently bioactivates compounds of the quinone family, such as mitomycin C. The observation that DTD is overexpressed in many cancerous tissues compared to normal tissues has provided us with a potentially selective target that can be exploited in the design of novel anticancer agents. Because of the relative lack of information on the cell-specific expression of DTD, the purpose of this study was to perform a body mapping of its normal distribution. Tissue samples from various components of the human reproductive system were analyzed by immunohistochemistry. We found strong expression of this enzyme in testicular stromal cells (Leydig cells) and in the epithelium of epididymis, ductuli efferentes, and Fallopian tube. These results suggest that DTD-bioactivated quinones could be responsible for a selective toxicity on these components of the reproductive system and cause clinical problems due to testosterone deficiency and infertility. This observation needs to be investigated in preclinical evaluation of new anticancer quinones and in patients treated with these compounds.