Skip Navigation

JNCI Journal of the National Cancer Institute 2001 93(20):1534-1540; doi:10.1093/jnci/93.20.1534
© 2001 by Oxford University Press
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 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 Request Permissions
Google Scholar
Right arrow Articles by Colussi, C.
Right arrow Articles by Bignami, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Colussi, C.
Right arrow Articles by Bignami, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Journal of the National Cancer Institute, Vol. 93, No. 20, 1534-1540, October 17, 2001
© 2001 Oxford University Press

ARTICLE

1,2-Dimethylhydrazine-Induced Colon Carcinoma and Lymphoma in msh2-/- Mice

Claudia Colussi, Silvia Fiumicino, Alessandro Giuliani, Sandra Rosini, Piero Musiani, Caterina Macrí, Christopher S. Potten, Marco Crescenzi, Margherita Bignami

C. Colussi, S. Fiumicino, A. Giuliani, C. Macrí, M. Crescenzi, M. Bignami, Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanitá, Rome, Italy; S. Rosini, P. Musiani, Department of Oncology and Neurosciences, G. D'Annunzio University, Chieti, Italy; C. S. Potten, Paterson Institute for Cancer Research, Christie Hospital Trust, Manchester, U.K.

Correspondence to: Margherita Bignami, Ph.D., Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanitá, Viale Regina Elena 299, 00161 Rome, Italy (e-mail: bignami{at}iss.it).

Background: Defective mismatch repair (MMR) in humans is particularly associated with familial colorectal cancer, but defective repair in mice is generally associated with lymphoma in the absence of experimental exposure to carcinogens. Loss of MMR also confers resistance to the toxic effects of methylating agents. We investigated whether resistance to methylation contributes to increased susceptibility to colorectal cancer in mice by exposing mice with defects in the MMR gene msh2 to a methylating agent. Methods: Tumor incidence and time of death in msh2+/+, msh2+/-, and msh2-/- mice were analyzed after weekly exposure (until tumor appearance) to the methylating agent 1,2-dimethylhydrazine (DMH). Chemically induced and spontaneous tumors were characterized by frequency, type, and location. The tumor incidence in untreated and treated mice of each genotype was compared by a Mann–Whitney U test. Carcinogen-induced apoptosis in histologic sections of small and large intestines was also determined. All statistical tests were two-sided. Results: Homozygous inactivation of the msh2 gene statistically significantly accelerated (P<.0001) death due to the development of DMH-induced colorectal tumors and lymphomas. Rates of death from DMH-induced colorectal adenocarcinoma were similar in msh2 heterozygous and wild-type mice, but only msh2 heterozygotes (msh+/-) developed additional, noncolorectal malignancies (notably trichofolliculoma [two of 21], angiosarcoma of the kidney capsule [two of 21], and lymphoma [one of 21]), suggesting that heterozygosity for msh2 slightly increases DMH susceptibility. DMH induced apoptosis in small intestinal and colonic epithelial crypts that was dependent on active msh2. Conclusions: Inactivation of msh2 allows the proliferation of gastrointestinal tract cells damaged by methylating agents. Furthermore, MMR constitutes a powerful defense against colorectal cancer induced by DNA methylation.


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
 Cancer Res.Home page
M. T. Russo, G. De Luca, I. Casorelli, P. Degan, S. Molatore, F. Barone, F. Mazzei, T. Pannellini, P. Musiani, and M. Bignami
Role of MUTYH and MSH2 in the Control of Oxidative DNA Damage, Genetic Instability, and Tumorigenesis
Cancer Res., May 15, 2009; 69(10): 4372 - 4379.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. R. Campbell, P. N. Nation, and S. E. Andrew
A Lack of DNA Mismatch Repair on an Athymic Murine Background Predisposes to Hematologic Malignancy
Cancer Res., April 1, 2005; 65(7): 2626 - 2635.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
J Thulesen, B Hartmann, K J Hare, H Kissow, C Orskov, J J Holst, and S S Poulsen
Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice
Gut, August 1, 2004; 53(8): 1145 - 1150.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. P. Lin, Y. Wang, S. J. Scherer, A. B. Clark, K. Yang, E. Avdievich, B. Jin, U. Werling, T. Parris, N. Kurihara, et al.
An Msh2 Point Mutation Uncouples DNA Mismatch Repair and Apoptosis
Cancer Res., January 15, 2004; 64(2): 517 - 522.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. J. Worrillow, L. B. Travis, A. G. Smith, S. Rollinson, A. J. Smith, C. P. Wild, E. J. Holowaty, B. A. Kohler, T. Wiklund, E. Pukkala, et al.
An Intron Splice Acceptor Polymorphism in hMSH2 and Risk of Leukemia after Treatment with Chemotherapeutic Alkylating Agents
Clin. Cancer Res., August 1, 2003; 9(8): 3012 - 3020.
[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.