Sensitivity of p53-deficient cells to oxaliplatin and thio-TEPA (N, N', N" triethylenethiophosphoramide).
P53 is known as a determinant of cellular responses to DNA damage, including apoptosis, cell cycle arrest, and DNA repair. Its role is most easily understood in the context of Burkitt lymphoma and other apoptosis-prone cell types. A number of epithelial cancer cell types, by contrast, exhibit a higher threshold for apoptosis induction in response to DNA damage. In fact, p53 mediates DNA repair and protective responses in the latter cell types, in some cases p53-deficient cells being more sensitive to DNA damage, antithetical to the situation in Burkitt lymphoma and other apoptosis-prone cell types. Ultraviolet light, cisplatin, and nitrogen mustards produce damage that is repaired by a p53-regulated pathway. Here, we explore the sensitivity of the platinum compound oxaliplatin and thio-TEPA (N, N', N", triethylenethiophosphoramide), a cancer chemotherapeutic agent that produces largely base damage, in p53-defective cells. This work demonstrates that the contribution of p53 temporally correlates with DNA repair pathways to produce a resistant phenotype, while the p53-defective cells are more sensitive to certain DNA-damaging chemotherapeutic agents.
Seo
Young R
YR
Department of Microbiology, Indiana University Cancer Center, Indiana University School of Medicine, Indianapolis, USA.
Chen
Edmund I-T
EI
Smith
Martin L
ML
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D013852:Thiotepa / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D016159:Tumor Suppressor Protein p53; D000077150:Oxaliplatin; D013852:Thiotepa