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 colorectal cancer (HNPCC). Loss of the wild-type allele generates a MMR-deficient cell compartment with a high propensity to oncogenic transformation. MMR deficiency not only accelerates spontaneous mutagenesis resulting from DNA replication errors, but also affects the cellular response to genotoxic agents. To study the consequences of MMR deficiency in vitro and to provide experimental access to HNPCC we have generated MMR-deficient cell lines and mice. The combination of MMR deficiency and exposure to genotoxic agents strongly accelerated lymphomagenesis.
Jansen
L
L
The Netherlands Cancer Institute, Division of Molecular Carcinogenesis, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Claij
N
N
Dekker
M
M
van Klink
Y
Y
van der Valk
M
M
van 't Wout
K
K
te Riele
H
H
D000818:Animals; D020137:Base Pair Mismatch / Q000235:genetics*; D002478:Cells, Cultured; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins; D020022:Genetic Predisposition to Disease; D008223:Lymphoma / Q000139:chemically induced / Q000235:genetics*; D051379:Mice; D051718:MutS Homolog 2 Protein; D009153:Mutagens / Q000633:toxicity*; D011518:Proto-Oncogene Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; D009153:Mutagens; D011518:Proto-Oncogene Proteins; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein