Tissue-specific activating mutations of Ha- and Ki-ras oncogenes in skin, lung, and liver tumors induced in mice following transplacental exposure to DMBA

Mol Carcinog. 1990;3(3):134-40. doi: 10.1002/mc.2940030306.

Abstract

Transplacental carcinogenesis represents a good model in which to study the involvement of tissue-specific oncogene activation in carcinogenesis because a single exposure to a carcinogen induces tumors at various sites. We tested tumors of the skin, liver, and lung produced in mice after transplacental 7,12-dimethylbenz[a]-anthracene (DMBA) exposure for possible activation of ras genes. XbaI restriction fragment-length polymorphism analysis has shown that exposure to DMBA in utero may result in appearance of A----T transversion at the second position of codon 61 of Ha-ras oncogene in skin and liver tumors but not in lung tumors. Moreover, DNA samples isolated from spontaneous and DMBA-induced lung and liver tumors were analyzed for mutations at the same position of Ki-ras oncogene using differential hybridization with specific oligonucleotides. Among five spontaneous lung tumors, three cases of A----G transition, and one case of A----T transversion were found, whereas four of ten lung tumors of DMBA-treated animals were positive for A----T mutation. No Ki-ras mutation was detected in one spontaneous and four DMBA-induced hepatomas. In two cases, we revealed Ki-ras A----T mutation in the lung tumor and Ha-ras mutation in the liver tumor taken from the same animal. These results indicate first that DMBA treatment may induce A----T mutation at the second position of codon 61 both in Ha-ras and in Ki-ras and, second, that the role of different activated oncogenes in carcinogenesis may differ, depending on the tissue in which the tumor develops.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Codon
  • Female
  • Fetal Diseases / chemically induced
  • Genes, ras*
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / genetics*
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / genetics*
  • Mice
  • Mutation*
  • Organ Specificity
  • Polymorphism, Restriction Fragment Length
  • Pregnancy
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / genetics*

Substances

  • Codon
  • 9,10-Dimethyl-1,2-benzanthracene