Abstract
Mouse skin tumors were produced after transplacental initiation [with 7,12-dimethylbenz(a)anthracene], only when the skin was treated post-natally with a tumor-promoting agent (12-O-tetradecanoyl phorbol 13-acetate). DNA analysis of tumors showed that all carcinomas analyzed contained a specific mutation (A to T transversion) at the 61st codon of c-Ha-ras. Fifty per cent of the papillomas analyzed also had this same mutation. The A to T transversion at the 61st codon of Ha-ras was heterozygous in all positive papillomas and carcinomas. No such mutation was found when benzo(a)pyrene was used as an initiating agent. These results indicate that fetal c-Ha-ras can be transplacentally activated through a specific point mutation by a carcinogen, but a cell harboring such a mutation may remain dormant until it encounters a tumor-promoting stimulus.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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9,10-Dimethyl-1,2-benzanthracene / administration & dosage
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9,10-Dimethyl-1,2-benzanthracene / toxicity*
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Animals
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Benzo(a)pyrene / toxicity
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Carcinoma / chemically induced*
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Carcinoma / genetics
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Cocarcinogenesis*
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DNA, Neoplasm / analysis
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Female
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Mice
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Mutation
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Papilloma / chemically induced*
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Papilloma / genetics
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Polymorphism, Restriction Fragment Length
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Pregnancy
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Prenatal Exposure Delayed Effects*
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins p21(ras)
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Proto-Oncogenes / drug effects*
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Skin Neoplasms / chemically induced*
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Skin Neoplasms / genetics
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Tetradecanoylphorbol Acetate / administration & dosage
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Tetradecanoylphorbol Acetate / toxicity*
Substances
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DNA, Neoplasm
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Proto-Oncogene Proteins
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Benzo(a)pyrene
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9,10-Dimethyl-1,2-benzanthracene
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Proto-Oncogene Proteins p21(ras)
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Tetradecanoylphorbol Acetate