Different inhibitory potential of sex hormones on NNK detoxification in vitro: a possible explanation for gender-specific lung cancer risk

Smoking women are probably at a higher risk to develop lung cancer than men. Different explanations exist for these findings, a gender-specific impairment of tobacco carcinogen metabolism being one of them. In this study, we examined the inhibition of NNK reduction to NNAL, the first and most important detoxication step of this tobacco-specific carcinogen. It is mediated by different carbonyl reductases of the SDR (CBR1 and 11βHSD1) and AKR (AKR1B10, AKR1C1, AKR1C2 and AKR1C4) superfamilies. Inhibition constants of NNK reduction were determined with male (testosterone) and female (estradiol, progesterone) sex hormones and the contraceptives ethinylestradiol and drospirenone in A549 cells and with purified enzymes.

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