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Publication : Diethylstilbestrol effects and lymphomagenesis in Mlh1-deficient mice.

First Author  Kabbarah O Year  2005
Journal  Int J Cancer Volume  115
Issue  4 Pages  666-9
PubMed ID  15700306 Mgi Jnum  J:98929
Mgi Id  MGI:3580744 Doi  10.1002/ijc.20918
Citation  Kabbarah O, et al. (2005) Diethylstilbestrol effects and lymphomagenesis in Mlh1-deficient mice. Int J Cancer 115(4):666-9
abstractText  Inherited defects in DNA mismatch repair (MMR) predispose to a variety of malignancies in humans and in mouse knockout models. In humans, hemizygosity for one of several DNA MMR genes greatly increases an individual's risk for colon and endometrial carcinoma. Hemizygous mice develop gastrointestinal tumors at a low to moderate frequency. Homozygous nulls have higher rates of gastrointestinal tumors and are particularly susceptible to lymphoma. In an effort to model endometrial carcinoma associated with mutation in MMR, we treated mice carrying knockout alleles for Mlh1 or Msh2 with the synthetic estrogen diethylstilbestrol (DES), a known promoter of uterine endometrial carcinoma. The C57BL/6 mice carrying DNA MMR mutations failed to develop endometrial carcinomas. However, the Mlh1-deficient mice treated with DES tended to become moribund at an early age and had very early onset of lymphoma. Comparison of DES-treated and untreated Mlh1-/- animals suggests the combination of Mlh1 deficiency and DES exposure accelerates lymphomagenesis.
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