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.
Laboratory of Nutritional and Molecular Regulation, Division of Basic Sciences, National Cancer Institute, Frederick, MD 21702-1201, USA.
J J
JJ
Mei
S D
SD
Hursting
S N
SN
Perkins
J M
JM
Phang
D000736:Androstenes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D015536:Down-Regulation; D002149:Energy Intake; D016158:Genes, p53 / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II
D000736:Androstenes; C066783:16-fluoro-5-androsten-17-one; D009569:Nitric Oxide; D003687:Dehydroepiandrosterone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse