p53-independent inhibition of nitric oxide generation by cancer preventive interventions in ex vivo mouse peritoneal macrophages.

We have previously reported that dietary interventions with purported anti-inflammatory activity delay spontaneous tumorigenesis in p53-deficient (p53-/-) mice. In the present study, 4 weeks of calorie restriction or the dietary administration of chemopreventive steroids dehydroepiandrosterone and 16alpha-fluoro-5-androsten-17-one significantly reduced the inducible generation of nitric oxide (NO) in ex vivo peritoneal macrophages from male p53 wild-type and p53-/- mice relative to the respective ad libitum-fed controls; expression of inducible nitric oxide synthase II (NOS2) protein was also markedly decreased compared with respective controls. These findings suggest that the p53-independent suppression of inducible NO production observed in this study may contribute to the anti-cancer effects of these preventive interventions in p53-/- mice.