Skip Navigation


ToxSci Advance Access originally published online on July 14, 2004
Toxicological Sciences 2004 81(2):293-301; doi:10.1093/toxsci/kfh226
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
81/2/293    most recent
kfh226v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Martin, K. R.
Right arrow Articles by French, J. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Martin, K. R.
Right arrow Articles by French, J. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences vol. 81 no. 2 © Society of Toxicology 2004; all rights reserved.

Tumor Profile of Novel p53 Heterozygous Tg.AC (v-Ha-ras) Bitransgenic Mice Treated with Benzo(a)pyrene and Fed Dietary N-acetyl-L-cysteine (NAC)

Keith R. Martin*,1, Micheal P. Jokinen{dagger}, Hayden P. Honeycutt{ddagger}, Anita Quinn{ddagger}, Frank W. Kari{ddagger}, J. Carl Barrett§ and John E. French{ddagger}

* Nutrition and Cancer Laboratory, Pennsylvania State University, University Park, Pennsylvania 16802; {dagger} Pathology Associates International, Durham, North Carolina 27709; {ddagger} Laboratory of Environmental Carcinogenesis & Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709; § Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Received May 17, 2004; accepted July 7, 2004

We designed a novel short-term bitransgenic model to better characterize the effects of benzo(a)pyrene (BP) exposure on multi-organ carcinogenesis and to evaluate the effects of a well-recognized antioxidant, N-acetyl-L-cysteine (NAC), on neoplasia. We selected the p53 heterozygous Tg.AC (v-Ha-ras) mouse model for our studies because these mice possess a carcinogen-inducible ras oncogene and one functional p53 tumor suppressor allele. Both mutations occur frequently in human cancers. In a 2 x 2 experimental design, both female and male mice were fed basal diet alone or containing 3% NAC and administered by gavage corn oil vehicle alone or containing 20 mg BP/kg body weight given twice weekly for 10 weeks. Mice (n = 15 for each grouping and sex) were subsequently observed an additional 18 weeks followed by tissue collection for evaluation of multi-organ pathology. Benzo(a)pyrene increased neoplasia in the thymus, spleen, stomach, and hematopoietic system after 28 weeks. We observed modest NAC-associated decreases in BP-induced pathology of the liver, papilloma formation and hyperplasia in the forestomach, and the occurrence of malignant lymphoma. Benzo(a)pyrene exposure reduced survival to ~40% in male mice, suggesting toxicity; however, survival in control groups was ~60%. Survival decreased to ~30% for females in all groups. We noted a clear, but nonsignificant, 15% decline in body weights of male, but not female, mice fed NAC, although food intake did not differ. Collectively, the data suggested carcinogen and antioxidant-associated effects on neoplasia that appeared sex-dependent. Thus, this novel short-term bitransgenic model may potentially be useful for testing dietary modulation of carcinogenesis.

Key Words: p53; Tg.AC; v-Ha-ras; antioxidant; NAC.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Balansky, F. D'Agostini, G. Ganchev, A. Izzotti, B. Di Marco, R. A. Lubet, N. Zanesi, C. M. Croce, and S. De Flora
Influence of FHIT on benzo[a]pyrene-induced tumors and alopecia in mice: Chemoprevention by budesonide and N-acetylcysteine
PNAS, May 16, 2006; 103(20): 7823 - 7828.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.