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001-es BibID:	BIBFORM015736
Első szerző:	Mabley, Jon G.
Cím:	Suppression of intestinal polyposis in Apcmin/+ mice by targeting the nitric oxide or poly(ADP-ribose) pathways / Mabley, J. G., Pacher, P., Bai, P., Wallace, R., Goonesekera, S., Virag, L., Southan, G. J., Szabo, C.
Dátum:	2004
ISSN:	0027-5107 (Print)
Megjegyzések:	Min mice have a germ-line nonsense mutation at codon 850 of the adenomatous polyposis coli (Apc) gene. These mice spontaneously develop multiple polyps in the small and large intestine at the age of 10-12 weeks. The aim of this study was to assess the role of reactive nitrogen species and poly(ADP-ribose) synthetase in tumorogenesis. Oxidative stress was found to be increased in the mucosa of the small intestine of Apc(min/+) mice with a concomitant increase in intestinal polyposis over control mice. Pharmacological inhibition of inducible nitric oxide synthase (NOS) with guanidinoethyldisulfide (GED) or stimulation of the breakdown of the nitrogen reactive species peroxynitrite using a potent decomposition catalyst, FP 15, reduced both the intestinal tumor load and the oxidative stress associated with intestinal polyposis in Apc(min/+) mice. Surprisingly, pharmacological inhibition of poly(ADP-ribose) synthetase by the phenanthridinone derivative PJ 34 also reduced the intestinal polyposis and oxidative stress in these mice, possibly through the inhibition of induction of nitric oxide synthase. These results suggest that reactive nitrogen species particularly peroxynitrite play a pivotal role in development of intestinal polyposis and that strategies to reduce both the oxidative stress and the formation of these radical species may be potential chemopreventive approaches for colorectal cancers.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Animals Colon/enzymology Enzyme Inhibitors/pharmacology Genes, APC/ physiology Guanidines/pharmacology Intestinal Mucosa/enzymology Intestinal Polyps/genetics/ metabolism/therapy Male Malondialdehyde/metabolism Metalloproteases/metabolism Mice Mice, Inbred C57BL Mice, Knockout Nitric Oxide/ metabolism Nitric Oxide Synthase/antagonists & inhibitors Nitric Oxide Synthase Type II Oxidative Stress Peroxynitrous Acid/metabolism Phenanthrenes/pharmacology Poly Adenosine Diphosphate Ribose/ metabolism Poly(ADP-ribose) Polymerases/antagonists & inhibitors/metabolism Signal Transduction
Megjelenés:	Mutation Research. - 548 : 1-2 (2004), p. 107-116. -
További szerzők:	Pacher Pál Bai Péter (1976-) (biokémikus) Wallace, R. Goonesekera, S. Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Southan, Garry J. Szabó Csaba
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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