Altered Expression of Oncogenes in Mouse Epidermis Following Exposure to Benzo(A)Pyrene Diol Epoxides

  • Jill C. Pelling
  • Sharon M. Ernst
  • George Patskan
  • Rodney S. Nairn
  • Douglas C. Hixson
  • Solon L. Rhode
  • Thomas J. Slaga
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)


There now exists a great deal of evidence which indicates that all normal eukaryotic cells contain endogenous, highly-conserved DNA sequences known as proto-oncogenes (1). The normal functions of these cellular oncogenes are not yet known, although it has been hypothesized that they may be important in cellular differentiation, fetal development and control of cell proliferation (2–4). Since a significant proportion of human cancers are presumed to be the result of exposure to environmental chemicals, extensive research efforts have focused on determining the effects of chemical carcinogens and tumor promoting agents on the expression of these c-onc sequences. Studies by Barbacid and coworkers using the rat mammary carcinoma model have shown that the Ha-ras oncogene is activated in rat mammary carcinomas induced by N-methylnitrosourea (5). Sequencing of the activated rat c-Ha-ras oncogene in individual mammary adenocarcinomas indicated that the rat proto-oncogene had undergone a point mutation in the 12th codon, resulting in a glycine-for-valine substitution in the ras P21 protein product. In similar studies, Balmain and Pragnell employed the two stage model of initiation and promotion in mouse skin to demonstrate that a percentage of papillomas and carcinomas induced by 7,12-dimethylbenz(a)anthracene (DMBA) and promotion with 12-0-tetradecanoyl phorbol-13acetate (TPA) contained elevated levels of Ha-ras transcripts compared with normal mouse epidermis. Furthermore, DNA from papillomas and squamous cell carcinomas caused morphological transformation of NIH/3T3 cells in vitro (6,7). Southern blot hybridization studies demonstrated that the transforming properties of the DNA were due to transfection of an activated cellular Ha-ras oncogene.


Skin Carcinogenesis Mouse Epidermis Cellular Oncogene Southern Blot Hybridization Analysis Pyrene Diol Epoxide 
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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Jill C. Pelling
    • 1
  • Sharon M. Ernst
    • 1
  • George Patskan
    • 2
  • Rodney S. Nairn
    • 2
  • Douglas C. Hixson
    • 3
  • Solon L. Rhode
    • 1
  • Thomas J. Slaga
    • 2
  1. 1.Eppley Institute for Research in Cancer and Allied DiseasesThe University of Nebraska Medical CenterOmahaUSA
  2. 2.The University of Texas System Cancer CenterSmithvilleUSA
  3. 3.Department of Medical OncologyRhode Island HospitalProvidenceUSA

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