Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis.
We have recently demonstrated that dramatic alteration in mucosal microvascular blood content termed early increase in blood supply (EIBS) is a hallmark of early colon carcinogenesis. In the current study, we elucidate the mechanism of EIBS by assessing iNOS/nitric oxide axis in the histologically normal colonic mucosa of rats treated with the colon-specific carcinogen, azoxymethane. We demonstrate that there was a strong temporal correlation between EIBS and iNOS expression/activity. Importantly, we also observed that short-term treatment with nitric oxide inhibitor abrogated EIBS. These data indicate that iNOS induction may have a critical role in augmenting the predysplastic mucosal blood supply and thereby fostering colon carcinogenesis.
Department of Medicine, Feinberg School of Medicine at Northwestern University, Section of Gastroenterology, Evanston-Northwestern Healthcare, G208 Evanston Hospital, 2650 Ridge Avenue, Evanston, IL 60201, USA. h-roy@northwestern.edu
Hemant K
HK
Roy
Ramesh K
RK
Wali
Young
Y
Kim
Yang
Y
Liu
John
J
Hart
Dhananjay P
DP
Kunte
Jennifer L
JL
Koetsier
Michael J
MJ
Goldberg
Vadim
V
Backman
D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000209:etiology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D008027:Light; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012542:Scattering, Radiation; D013997:Time Factors
D002273:Carcinogens; D004791:Enzyme Inhibitors; D052247:Nitric Oxide Synthase Type II; D001397:Azoxymethane; D019331:NG-Nitroarginine Methyl Ester