H-ras mutations at codon 61 or 13 in tumors initiated with a NO donor in mouse skin.
The tumor-initiating activity of nitric oxide (NO) in carcinogenesis was assessed using (+/-)-(E)-4-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexenamide (NOR1), a synthetic NO donor. Topical application of NOR1 followed by 12-O-tetradecanoylphorbol 13-acetate (TPA) treatment twice a week for 20 weeks resulted in the development of papillomas in mice. All of the papillomas examined contained H-ras mutations at codons 61 or 13. At codon 61, CAA-CTA and CAA-TTA mutations were seen in 42/46 and 1/46 of the papillomas, respectively. Three papillomas without a mutation at codon 61 were mutated at codon 13. A GGC-CGC mutation was found in two of these samples while the third possessed a GGC-GTC mutation. These results suggest that NO possesses tumor-initiating activity through a process that induces mutation in H-ras.
Satomi
Yoshiko
Y
Department of Biochemistry, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Bu
Ping
P
Okuda
Masato
M
Tokuda
Harukuni
H
Nishino
Hoyoku
H
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens; D003062:Codon; D005260:Female; D011905:Genes, ras; D051379:Mice; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism*; D009574:Nitro Compounds / Q000494:pharmacology; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate
D002273:Carcinogens; D003062:Codon; D009574:Nitro Compounds; C101316:methyl-2-hydroxyimino-5-nitro-6-methoxy-3-hexeneamide; D009569:Nitric Oxide; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate