Acceleration of lymphomagenesis in mismatch-repair deficient mice by exposure to genotoxic agents

Hemizygosity for genes that are essential for DNA mismatch repair (MMR) was found to underlie cancer predisposition in hereditary nonpolypsis colorect al cancer (HNPCC). Loss of the wild-type allele generates a MMR-deficient c ell compartment with a high propensity to oncogenic transformation. MMR def iciency not only accelerates spontaneous mutagenesis resulting from DNA rep lication errors, but also affects the cellular response to genotoxic agents . To study the consequences of MMR deficiency in vitro and to provide exper imental access to HNPCC we have generated MMR-deficient cell lines and mice . The combination of MMR deficiency and exposure to genotoxic agents strong ly accelerated lymphomagenesis. (C) 2000 Published by Elsevier Science Irel and Ltd. All rights reserved.