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Tumor Spectrum in the p53 Heterozygous Zeta Globin-Promoted Tg.AC (v-Ha-ras) Bitransgenic Mouse Model

Laboratory of Environmental Carcinogenesis & Mutagenesis, NIEHS, Research Triangle Park, North Carolina, krm12{at}psu.edu

Michael P. Jokinen

Pathology Associates International, Durham, North Carolina

Hayden P. Honeycutt

Laboratory of Environmental Carcinogenesis & Mutagenesis, NIEHS, Research Triangle Park, North Carolina

Anita Quinn

Laboratory of Environmental Carcinogenesis & Mutagenesis, NIEHS, Research Triangle Park, North Carolina

Frank W. Kari

Laboratory of Environmental Carcinogenesis & Mutagenesis, NIEHS, Research Triangle Park, North Carolina

J. Carl Barrett

Laboratory of Molecular Carcinogenesis, NIEHS, Research Triangle Park, North Carolina

John E. French

Laboratory of Environmental Carcinogenesis & Mutagenesis, NIEHS, Research Triangle Park, North Carolina

The use of a bitransgenic mouse model for cancer is an effective approach for studying the impact of specific carcinogens and the occurrence of tissue-specific lesions. We studied the novel p53 heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) mouse model because these mice contain a carcinogen-inducible ras oncogene and one functional p53 tumor suppressor allele, both of which occur frequently in human cancers. Our aim was to characterize the short-term control and chemically induced tumor spectrum in this novel model. Mice were placed on basal semipurified diet containing 20% soy protein for 2 weeks prior to random allocation to groups. Subsequently, 15 male and 15 female mice were administered corn oil vehicle alone or containing benzo(a)pyrene (20 mg/kg body weight) via oral gavage 2 times per week for 10 weeks with subsequent observation for 18 weeks. Mice exhibited lesions characteristic of FVB/N, p53 heterozygous and Tg.AC mouse models. However, an array of unique, novel lesions were observed including uterine leiomyosarcomas, mammary gland carcinomas, mammary squamous cell carcinomas, and parotid salivary gland carcinomas suggesting tissue-specific interactions of the 2 genotypes. Thus, this bitransgenic model may provide further insight into the mechanistic interaction of 2 genes commonly mutated in neoplasia.

Key Words: p53 heterozygote • Tg.AC • v-Ha-ras • bitransgenic • zeta globin • benzo(a)pyrene.

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Toxicologic Pathology, Vol. 32, No. 4, 418-425 (2004)
DOI: 10.1080/01926230490462129


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Martin, K. R. Articles by French, J. E. Search for Related Content PubMed PubMed Citation Articles by Martin, K. R. Articles by French, J. E. Social Bookmarking                         What's this?