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-defi cient (p53(-/-)) mice. In the present study, 4 weeks of calorie restri ction or the dietary administration of chemopreventive steroids dehydr oepiandrosterone and 16 alpha-fluoro-5-androsten-17-one significantly reduced the inducible generation of nitric oxide (NO) in ex vivo perit oneal macrophages from male p53 wild-type and p53(-/-) mice relative t o the respective ad libitum-fed controls; expression of inducible nitr ic oxide synthase II (NOS2) protein was also markedly decreased compar ed with respective controls. These findings suggest that the p53-indep endent suppression of inducible NO production observed in this study m ay contribute to the anti-cancer effects of these preventive intervent ions in p531(-/-) mice. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved.