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Codon 61 Mutations in the c‐Harvey‐ ras Gene in Mouse Skin Tumors Induced by 7,12‐Dimethylbenz[ a ]anthracene Plus Okadaic Acid Class Tumor Promoters
Author(s) -
Fujiki Hirota,
Suganuma Masami,
Yoshizawa Shigeru,
Kanazawa Hiroshi,
Sugimura Takashi,
Manam Sujata,
Kahn Scott M.,
Jiang Wei,
Hoshina Sadayori,
Weinstein I. Bernard
Publication year - 1989
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940020403
Subject(s) - okadaic acid , dmba , promoter , biology , microbiology and biotechnology , carcinogenesis , 12 o tetradecanoylphorbol 13 acetate , gene , 7,12 dimethylbenz[a]anthracene , tetradecanoylphorbol acetate , dna , biochemistry , gene expression , phosphatase , phosphorylation , phorbol ester , protein kinase c
Three okadaic acid class tumor promoters, okadaic acid, dinophysistoxin‐1, and calyculin A, have potent tumor‐promoting activity in two‐stage carcinogenesis experiments on mouse skin. DNA isolated from tumors induced by 7,12‐dimethylbenz[ a ]anthracene (DMBA) and each of these tumor promoters revealed the same mutation at the second nucleotide of codon 61 (CAA → CTA) in the c‐Ha‐ ras gene, determined by the polymerase chain reaction procedure and DNA sequencing. Three potent 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA)‐type tumor promoters, TPA, teleocidin, and aplysiatoxin, showed the same effects. These results provide strong evidence that this mutation in the c‐Ha‐ ras gene is due to a direct effect of DMBA rather than a selective effect of specific tumor promoters.