Possible involvement of NO-mediated oxidative stress in induction of rat forestomach damage and cell proliferation by combined treatment with catechol and sodium nitrite.
To clarify the mechanisms underlying forestomach carcinogenesis in rats by co-treatment with catechol and sodium nitrite (NaNO2), we investigated the involvement of oxidative stress resulting from reaction of the two compounds. Since generation of semiquinone radical, hydroxyl radical (*OH), and peroxynitrite (ONOO-) arose through the reaction of catechol with NO, we proposed that superoxide resulting from catechol oxidation reacted with excess NO, consequently yielding *OH via ONOO-. Male F344 rats were co-treated with 0.2% catechol in the diet and 0.8% NaNO2 in the drinking water for 2 weeks. Prior to occurrence of histological evidence indicating epithelial injury and hyperplasia, 8-hydroxydeoxyguanosine levels in forestomach epithelium significantly increased from 12 h together with appearance of immunohistochemically nitrotyrosine-positive epithelial cells. There were no remarkable changes in rats given each chemical alone. We conclude that oxidative stress due to NO plays an important role in induction of forestomach epithelial damage, cell proliferation, and thus presumably forestomach carcinogenesis.
Ishii
Yuji
Y
Department of Analytical Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Umemura
Takashi
T
Kanki
Keita
K
Kuroiwa
Yuichi
Y
Nishikawa
Akiyoshi
A
Ito
Rie
R
Saito
Koichi
K
Nakazawa
Hiroyuki
H
Hirose
Masao
M
D000284:Administration, Oral; D000818:Animals; D002396:Catechols / Q000008:administration & dosage / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D004338:Drug Combinations; D005753:Gastric Mucosa / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000633:toxicity*; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology
D002396:Catechols; D004338:Drug Combinations; D009569:Nitric Oxide; C034221:catechol; D012977:Sodium Nitrite