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.
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.
Fujiki
H
H
National Cancer Center Research Institute, Tokyo, Japan.
Suganuma
M
M
Yoshizawa
S
S
Kanazawa
H
H
Sugimura
T
T
Manam
S
S
Kahn
S M
SM
Jiang
W
W
Hoshina
S
S
Weinstein
I B
IB
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002273:Carcinogens / Q000145:classification / Q000494:pharmacology*; D003062:Codon; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004259:DNA-Directed DNA Polymerase; D004988:Ethers, Cyclic / Q000494:pharmacology; D011905:Genes, ras / Q000187:drug effects*; D008297:Male; D051379:Mice; D019319:Okadaic Acid; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000235:genetics; D019914:Taq Polymerase
D002273:Carcinogens; D003062:Codon; D004273:DNA, Neoplasm; D004988:Ethers, Cyclic; D012333:RNA, Messenger; D019319:Okadaic Acid; D015127:9,10-Dimethyl-1,2-benzanthracene; D019914:Taq Polymerase; D004259:DNA-Directed DNA Polymerase