title: Possible involvement of NO-mediated oxidative stress in induction of rat forestomach damage and cell proliferation by combined treatment with catechol and sodium nitrite.
abstract: 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.
authors.affiliation: Department of Analytical Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishii
authors.forename: Takashi
authors.initials: T
authors.lastname: Umemura
authors.forename: Keita
authors.initials: K
authors.lastname: Kanki
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kuroiwa
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
authors.forename: Rie
authors.initials: R
authors.lastname: Ito
authors.forename: Koichi
authors.initials: K
authors.lastname: Saito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakazawa
authors.forename: Masao
authors.initials: M
authors.lastname: Hirose
mesh_terms: 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
chemical_list: D002396:Catechols; D004338:Drug Combinations; D009569:Nitric Oxide; C034221:catechol; D012977:Sodium Nitrite