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Publication : Frequent p53 and H-ras mutations in benzene- and ethylene oxide-induced mammary gland carcinomas from B6C3F1 mice.

First Author  Houle CD Year  2006
Journal  Toxicol Pathol Volume  34
Issue  6 Pages  752-62
PubMed ID  17162533 Mgi Jnum  J:134714
Mgi Id  MGI:3789558 Doi  10.1080/01926230600935912
Citation  Houle CD, et al. (2006) Frequent p53 and H-ras mutations in benzene- and ethylene oxide-induced mammary gland carcinomas from B6C3F1 mice. Toxicol Pathol 34(6):752-62
abstractText  Benzene and ethylene oxide are multisite carcinogens in rodents and classified as human carcinogens by the National Toxicology Program. In 2-year mouse studies, both chemicals induced mammary carcinomas. We examined spontaneous, benzene-, and ethylene oxide-induced mouse mammary carcinomas for p53 protein expression, using immunohistochemistry, and p53 (exons 5-8) and H-ras (codon 61) mutations using cycle sequencing techniques. p53 protein expression was detected in 42% (8/19) of spontaneous, 43% (6/14) of benzene-, and 67% (8/12) of ethylene oxide-induced carcinomas. However, semiquantitative evaluation of p53 protein expression revealed that benzene- and ethylene oxide-induced carcinomas exhibited expression levels five- to six-fold higher than spontaneous carcinomas. p53 mutations were found in 58% (7/12) of spontaneous, 57% (8/14) of benzene-, and 67% (8/12) of ethylene oxide-induced carcinomas. H-ras mutations were identified in 26% (5/19) of spontaneous, 50% (7/14) of benzene-, and 33% (4/12) of ethylene oxide-induced carcinomas. When H-ras mutations were present, concurrent p53 mutations were identified in 40% (2/5) of spontaneous, 71% (5/7) of benzene-, and 75% (3/4) of ethylene oxide-induced carcinomas. Our results demonstrate that p53 and H-ras mutations are relatively common in control and chemically induced mouse mammary carcinomas although both chemicals can alter the mutational spectra and more commonly induce concurrent mutations.
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