PMID: 11604476Oct 18, 2001Paper

1,2-Dimethylhydrazine-induced colon carcinoma and lymphoma in msh2(-/-) mice

Journal of the National Cancer Institute
C ColussiM Bignami

Abstract

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. 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. 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 ad...Continue Reading

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Citations

Sep 1, 2006·Digestive Diseases and Sciences·Tadahisa FukuiSumio Kawata
Jan 17, 2004·Biochimie·Peter KarranMargherita Bignami
Nov 6, 2003·Toxicology·Susan W P Wijnhoven, Harry van Steeg
Oct 3, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M BignamiP Karran
Jun 14, 2002·Current Biology : CB·Claudia ColussiMargherita Bignami
Jul 13, 2002·Trends in Molecular Medicine·Kaichun WeiWinfried Edelmann
Sep 7, 2005·Pharmacogenomics·James M Allan, Charles S Rabkin
Dec 9, 2004·Biochimica Et Biophysica Acta·Joanna Zabkiewicz, Alan R Clarke
Jun 18, 2016·Archives of Toxicology·Aya M WestbrookRobert H Schiestl
Jul 21, 2004·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Lisa Edelmann, Winfried Edelmann
Dec 29, 2005·International Journal of Cancer. Journal International Du Cancer·Shanbeh ZienolddinyAage Haugen
Jan 28, 2004·Cancer Research·Diana P LinWinfried Edelmann
Mar 4, 2003·Gastroenterology·Gregory P BoivinRobert J Coffey
Mar 6, 2009·Gastroenterology·Makoto Mark Taketo, Winfried Edelmann

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