Premium
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
Author(s) -
Digiovanni John,
Beltrán Linda,
Rupp Amy,
Gill Rosalynn D.,
Harvey Ronald G.
Publication year - 1993
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940080410
Subject(s) - transversion , biology , mutation , microbiology and biotechnology , gene , benzo(a)pyrene , genetics , carcinogen
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 A 182 →T and A 182 →G mutations. In addition, one promoter‐induced tumor had a G 35 →A mutation in codon 12, and one had a G 37 °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 G 37 °C transversion and two had G 38 → 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 A 182 → T transversions in codon 61 except for two 7‐MBA—initiated papillomas that had G 37 °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.