@article{cullen_williams_zadrozny_otstot_solomon_sills_hong_2011, title={H-ras Consensus Sequence and Mutations in Primary Hepatocellular Carcinomas of Lemurs and Lorises}, volume={48}, ISSN={["0300-9858"]}, DOI={10.1177/0300985810388526}, abstractNote={ The authors have determined a consensus sequence for exons 1 and 2 of H -ras from captive lemurs and lorises and evaluated samples of nonneoplastic liver and hepatocellular carcinomas (HCC) from affected animals for mutations in these exons. Frozen liver samples were collected from 20 animals representing 9 different species with a sex distribution of 10 males and 10 females. A total of 26 liver samples, including 11 normal livers, 9 HCC, and 6 samples from nonneoplastic regions of liver from animals with HCC, were evaluated. This is the first report of the consensus sequence for exons 1 and 2 of H- ras in prosimians, and the authors have determined that it is identical to that of human H- ras and differs only slightly from the chimpanzee sequence. Point mutations were identified in 6 of the 9 HCC samples examined with codons 7, 22, 32, 56, 61, 84, and 96 affected. Two carcinomas had double mutations, and one tumor had triple mutations. One HCC had a mutation in codon 61, which is identical to a recognized affected codon for an H- ras “hot spot” in rodent neoplasia that has also been reported in human tumors. Although not statistically different, metastasis occurred in 5 of 6 HCC with H- ras mutation and only 1 of 3 HCC without mutations. There were 4 silent mutations that did not contain changes in the encoded amino acids, 2 of which were found in nonneoplastic regions of tumor-bearing liver. }, number={4}, journal={VETERINARY PATHOLOGY}, author={Cullen, J. M. and Williams, C. and Zadrozny, L. and Otstot, J. T. and Solomon, G. G. and Sills, R. C. and Hong, H-H. L.}, year={2011}, month={Jul}, pages={868–874} } @article{houle_ton_clayton_huff_hong_sills_2006, title={Frequent p53 and H-ras mutations in benzene- and ethylene oxide-induced mammary gland carcinomas from B6C3F1 mice}, volume={34}, ISSN={["0192-6233"]}, DOI={10.1080/01926230600935912}, abstractNote={ 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. }, number={6}, journal={TOXICOLOGIC PATHOLOGY}, author={Houle, Christopher D. and Ton, Thai-Vu T. and Clayton, Natasha and Huff, James and Hong, Hue-Hua L. and Sills, Robert C.}, year={2006}, pages={752–762} }