Mutagenicity of 8-nitroguanosine, a product of nitrative nucleoside modification by reactive nitrogen oxides, in mammalian cells.
8-Nitroguanosine is a nitratively modified nucleoside that is formed endogeneously under inflammatory conditions dependent on nitric oxide production, particularly associated with cancer risks. Here, we investigated the mutagenic potential of 8-nitroguanosine in mammalian cells. Treatment with 8-nitroguanosine (10-1000 microM) for 1h significantly increased (by 6-8 times) the mutation frequency of the xanthine-guanine phosphoribosyltransferase (gpt) gene in AS52 cells without cytotoxic effects. 8-Nitroguanosine treatment induced a G-to-T transversion in gpt gene at position 86. It also significantly increased levels of abasic sites in DNA. These observations suggest that formation of 8-nitroguanosine may contribute to the pathogenesis of inflammation-associated carcinogenesis.
Kaneko
Kazuyoshi
K
Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Akuta
Teruo
T
Sawa
Tomohiro
T
Kim
Ha Won
HW
Fujii
Shigemoto
S
Okamoto
Tatsuya
T
Nakayama
Hitoshi
H
Ohigashi
Hajime
H
Murakami
Akira
A
Akaike
Takaaki
T
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D006151:Guanosine / Q000031:analogs & derivatives* / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009574:Nitro Compounds / Q000633:toxicity*; D009589:Nitrogen Oxides / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics
C481144:8-nitroguanosine; D009153:Mutagens; D009574:Nitro Compounds; D009589:Nitrogen Oxides; D006151:Guanosine; D017855:Transferases (Other Substituted Phosphate Groups); C106504:UDP-GlcNAc-undecaprenyl phosphate N-acetylglucosaminyl 1-phosphate transferase