INVOLVEMENT OF THE MISMATCH REPAIR SYSTEM IN TEMOZOLOMIDE-INDUCED APOPTOSIS
作者： Stefania D’Atri , Lucio Tentori , Pedro Miguel Lacal , Grazia Graziani , Elena Pagani
DOI: 10.1124/MOL.54.2.334
关键词: Biology 、 DNA fragmentation 、 Etoposide 、 Apoptosis 、 Temozolomide 、 Topoisomerase-II Inhibitor 、 DNA mismatch repair 、 Molecular biology 、 Cancer research 、 Cell culture 、 Cell growth
摘要: Postreplicative mismatch repair plays a major role in mediating the cytotoxicity of agents generating O6-methylguanine DNA. We previously showed that methylating antitumor triazene compound, temozolomide, induces apoptosis and persistence DNA is required to trigger process. wanted test whether latter apoptotic signal dependent on functional system. To this end, we used two human lymphoblastoid cell lines (i.e., repair-proficient TK6 line its repair-deficient subline MT1) are both deficient repair. Temozolomide treatment cells brought about efficient growth inhibition, G2/M arrest, apoptosis, as indicated by results cytofluorimetric analysis 5-bromo-2'-deoxyuridine incorporation content evaluation fragmentation. The drug resulted also induction p53 p21/waf-1 protein expression. In contrast, MT1 were highly resistant no was observed. Importantly, could show not p53-dependent pathway; with etoposide, topoisomerase II inhibitor, expression lines. conclusion, demonstrate existence link between system exposed clinically relevant concentrations temozolomide. suggest response O6-guanine methylation involves
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