Different effects of methotrexate on DNA mismatch repair proficient and deficient cells. (Articolo in rivista)

Type
Label
  • Different effects of methotrexate on DNA mismatch repair proficient and deficient cells. (Articolo in rivista) (literal)
Anno
  • 2001-01-01T00:00:00+01:00 (literal)
Alternative label
  • Frouin I, Prosperi E, Denegri M, Negri C, Donzelli M, Rossi L, Riva F, Stefanini M, Scovassi AI. (2001)
    Different effects of methotrexate on DNA mismatch repair proficient and deficient cells.
    in European journal of cancer (1965)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Frouin I, Prosperi E, Denegri M, Negri C, Donzelli M, Rossi L, Riva F, Stefanini M, Scovassi AI. (literal)
Pagina inizio
  • 1173 (literal)
Pagina fine
  • 1180 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 37 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Istituto di Genetica Biochimica ed Evoluzionistica del CNR, Pavia; Centro di Studio per l'Istochimica del CNR, Pavia (literal)
Titolo
  • Different effects of methotrexate on DNA mismatch repair proficient and deficient cells. (literal)
Abstract
  • Antifolates exert their antiproliferative activity through the inhibition of dihydrofolate reductase and, as a consequence, of thymidylate synthesis, thereby inducing nucleotide misincorporation and impairment of DNA synthesis. We investigated the processes involved in the repair of antifolate-induced damage and their relationship with cell death. Since misincorporated bases may be removed by DNA mismatch repair (MMR), the study was carried out on the MMR-proficient human cell lines HeLa and HCT116+chr3, and, in parallel, on the MMR-deficient cell lines HeLa cell-clone12, defective in the protein hPMS2, and HCT116, with an inactive hMLH1. After treatment with methotrexate (MTX), we observed that DNA repair synthesis occurs independently of the cellular MMR function. Clear signs of apoptosis such as nuclear shrinkage, chromatin condensation and degradation, DNA laddering, and poly (ADP-ribose) polymerase (PARP) proteolysis, were visible in both MMR(+) and MMR(-) cells. Remarkably, cell viability was lower and the apoptotic process was triggered more efficiently in the MMR-competent cells. (literal)
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