期刊
CANCER LETTERS
卷 196, 期 1, 页码 17-22出版社
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0304-3835(03)00188-5
关键词
nitric oxide; carcinogenesis; H-ras; initiator; mutation
类别
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. (C) 2003 Elsevier Science Ltd. All rights reserved.
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