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Nitric oxide is an effector molecule in inhibition of tumor cell growth by rIFN‐γ‐activated rat neutrophils
Author(s) -
Yamashita Takao,
Uchida Tetsuro,
Araki Akemi,
Sendo Fujiro
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970410)71:2<223::aid-ijc17>3.0.co;2-i
Subject(s) - cytostasis , nitric oxide , chemistry , superoxide dismutase , interferon gamma , free radical scavenger , reactive oxygen species , biochemistry , in vitro , cytotoxicity , enzyme , antioxidant , organic chemistry
This study was designed to determine the effector molecule responsible for the tumor‐inhibitory activity of rat neutrophils treated with rat recombinant interferon gamma (rIFN‐γ) in vitro . The results show that nitric oxide (NO) production by neutrophils is dependent on rIFN‐γ concentration, and that neutrophil‐mediated tumor cytostasis is in turn dependent on the amount of NO. NO production and tumor cytostatis by rIFN‐γ‐activated neutrophils were inhibited completely by N G monomethyl‐L‐arginine (N G MMA), a specific competitive NO production inhibitor. Tumor cytostasis was also inhibited by oxyhemoglobin (HbO 2 ), an NO scavenger. An extracellular oxygen radical scavenger, superoxide dismutase (SOD), was found to increase tumor cell inhibition by rIFN‐γ‐activated neutrophils by a factor of 4. This SOD‐enhanced cytostasis was not even inhibited by catalase. Tumor cytostasis was slightly increased by a hydroxyl radical‐(‐OH) scavanger, dimethylthiourea (DMTU), which did not affect NO production by rIFN‐γ‐activated neutrophils. Our findings suggest that tumor cytostasis of neutrophils activated by rIFN‐γ is mediated by L‐arginine‐derived nitrogen oxidation products, and that O 2 − produced by these neutrophils reduces NO‐mediated tumor cytostasis at low NO concentrations. Int. J. Cancer 71:223‐230, 1997. © 1997 Wiley‐Liss, Inc.