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Administration of methylnitrosourea (MNU) to female rats during or before puberty induces a high incidence of mammary tumors, most of which contain a G to A transition at the second base of H-ras codon 12. However, this mutation alone is presumably not sufficient for normal mammary epithelial cells to develop into neoplastic cells, because it can be detected in mammary tissues prior to the appearance of tumors. To clarify whether p53 genetic changes may complement the H-ras mutation in mammary carcinogenesis, we investigated nine MNU-induced mammary tumors of F344 rats by polymerase chain reaction-mediated denaturing gradient gel electrophoresis (DGGE). However, no mutations were identified in p53 exons 5 through 8, which include the known mutational hot spots. Our data thus indicate that p53 mutations are not involved in MNU-induced rat mammary carcinogenesis.
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