TY - JOUR
T1 - Sensitivity of p53-deficient cells to oxaliplatin and thio-tepa (n, n′, n′ triethylenethiophosphoramide)
AU - Seo, Young R.
AU - Chen, Edmund I.T.
AU - Smith, Martin L.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Chemosensitivity
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=0036010914&partnerID=8YFLogxK
U2 - 10.1023/A:1014913708916
DO - 10.1023/A:1014913708916
M3 - Article
C2 - 12058967
AN - SCOPUS:0036010914
SN - 0167-6806
VL - 72
SP - 255
EP - 263
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -