Further analysis of c-Ha-ras mutations in papillomas initiated by several polycyclic aromatic hydrocarbons and papillomas from uninitiated, promoter-treated skin in SENCAR mice

Mol Carcinog. 1993;8(4):272-9. doi: 10.1002/mc.2940080410.


In this study we analyzed the mutations in c-Ha-ras from skin papillomas initiated with benzo[a]pyrene (B[a]P), 7-methylbenz[a]anthracene (7-MBA), and 10-fluoro-7-methylbenz[a]anthracene (10-F-7-MBA) and from papillomas induced by treatment with tumor promoter alone. Among the papillomas induced by treatment with tumor promoter alone, 56% (nine of 16) had mutations in c-Ha-ras. These mutations were found primarily in codon 61 and included both A182-->T and A182-->G mutations. In addition, one promoter-induced tumor had a G35-->A mutation in codon 12, and one had a G37-->C mutation in codon 13. The other promoter-induced papillomas did not have detectable mutations in codons 12, 13, or 61. Most of the B[a]P-initiated papillomas (77%; 10 of 13) did not have detectable mutations in c-Ha-ras codons 12, 13, or 61. However, three of these B[a]P-initiated papillomas had c-Ha-ras codon 13 mutations; one had a G37-->C transversion and two had G38-->T transversions. Most of the 7-MBA-initiated tumors and all of the 10-F-7-MBA-initiated tumors had an activated c-Ha-ras gene [nine of 10 (90%) and 11 of 11 (100%), respectively]. These mutations were almost exclusively A182-->T transversions in codon 61 except for two 7-MBA-initiated papillomas that had G37-->C transversions in codon 13. The results suggest that more than one mechanism may contribute to activation of c-Ha-ras by polycyclic aromatic hydrocarbons (PAHs) in mouse skin. Furthermore, the absence of c-Ha-ras mutations in most B[a]P-initiated papillomas, as well as in a significant fraction of those induced by tumor promoter alone, suggests that there may be other molecular targets involved in tumor initiation by PAHs in mouse skin.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Benz(a)Anthracenes
  • Benzo(a)pyrene
  • Carcinogens*
  • Codon / genetics
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / genetics
  • Female
  • Genes, ras / genetics*
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Mutation* / drug effects
  • Papilloma / chemically induced*
  • Papilloma / genetics*
  • Polycyclic Compounds*
  • Skin / drug effects
  • Skin Neoplasms / chemically induced*
  • Skin Neoplasms / genetics*
  • Skin Physiological Phenomena


  • Benz(a)Anthracenes
  • Carcinogens
  • Codon
  • DNA, Neoplasm
  • Polycyclic Compounds
  • Benzo(a)pyrene
  • 7-methylbenzanthracene