Mice defective in the mismatch repair gene Msh2 show increased predisposition to UVB radiation-induced skin cancer.
Mice defective in the mismatch repair (MMR) gene Msh2 manifest an enhanced predisposition to skin cancer associated with exposure to UVB radiation. This predisposition is further heightened if the mice are additionally defective for the nucleotide excision repair gene Xpc. To test the hypothesis that the predisposition of Msh2 mutant mice to skin cancer reflects a mutator phenotype associated with increased proliferation of skin cells following exposure to UV radiation, Msh2 mutant mice were exposed to the tumor promoter TPA. Such mice showed a robust proliferative response in the skin, but did not manifest evidence of dysplasia or neoplasia. We conclude that the predisposition of Msh2 mice to UVB radiation-induced skin cancer reflects an interaction between the processes of mismatch repair and some other excision repair mode, the exact nature of which remains to be established.
Meira
Lisiane B
LB
Laboratory of Molecular Pathology, Department of Pathology, Southwestern Medical Center, University of Texas, Dallas, TX 75235, USA.
Cheo
David L
DL
Reis
Antonio M
AM
Claij
Nanna
N
Burns
Dennis K
DK
te Riele
Hein
H
Friedberg
Errol C
EC
D000818:Animals; D020137:Base Pair Mismatch / Q000235:genetics*; D002273:Carcinogens / Q000494:pharmacology; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D051718:MutS Homolog 2 Protein; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012867:Skin / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014466:Ultraviolet Rays
D002273:Carcinogens; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C501002:Xpc protein, mouse; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein; D013755:Tetradecanoylphorbol Acetate