Transplacental induction of a specific mutation in fetal Ha-ras and its critical role in post-natal carcinogenesis

Int J Cancer. 1987 Dec 15;40(6):818-22. doi: 10.1002/ijc.2910400619.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / administration & dosage
  • 9,10-Dimethyl-1,2-benzanthracene / toxicity*
  • Animals
  • Benzo(a)pyrene / toxicity
  • Carcinoma / chemically induced*
  • Carcinoma / genetics
  • Cocarcinogenesis*
  • DNA, Neoplasm / analysis
  • Female
  • Mice
  • Mutation
  • Papilloma / chemically induced*
  • Papilloma / genetics
  • Polymorphism, Restriction Fragment Length
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Proto-Oncogenes / drug effects*
  • Skin Neoplasms / chemically induced*
  • Skin Neoplasms / genetics
  • Tetradecanoylphorbol Acetate / administration & dosage
  • Tetradecanoylphorbol Acetate / toxicity*

Substances

  • DNA, Neoplasm
  • Proto-Oncogene Proteins
  • Benzo(a)pyrene
  • 9,10-Dimethyl-1,2-benzanthracene
  • Proto-Oncogene Proteins p21(ras)
  • Tetradecanoylphorbol Acetate