Nucleotide Excision Repair-deficient Human Cells in Culture Exhibit Decreased Survival After 2-chlorodeoxyadenosine Treatment
Document Type
Article
Publication Title
Anticancer Research
Abstract
2-Chloro-2'-deoxyadenosine (CldAdo, cladribine) is a clinically important nucleoside analog for adult and pediatric leukemias. We previously described an activity in HeLa cell nuclear extracts that specifically recognized CldAMP-substituted oligomers. The factor was present in extracts prepared from repair-deficient xeroderma pigmentosum (XP) complementation group A cells, but not from group E--which are defective in damaged DNA-binding (DDB) protein--suggesting a possible repair process for incorporated analogs. Here we examined XP lymphoblast survival after CldAdo treatment using a cell proliferation assay. Control CEM leukemia cells and immortalized normal human lymphoblasts exhibited similar cytotoxicity profiles at each concentration tested. However, a 2.1-fold increase in sensitivity to CldAdo was detected in XP-E (5) cells lacking a functional DDB subunit. XP-A, XP-D and XP-G cell lines also had increased sensitivity to CldAdo, ranging from 1.61- to 1.91-fold greater compared to normal lymphoblasts. Our findings suggest that the clinical efficacy of CldAdo may be attenuated by repair mechanisms that target and remove such altered nucleic acids from cellular DNA.
Publication Date
7-2003
ISSN
1791-7530
Recommended Citation
Lawrenzi J, Bunnell A, Hentosh P. Nucleotide Excision Repair-deficient Human Cells in Culture Exhibit Decreased Survival After 2-chlorodeoxyadenosine Treatment. Anticancer Research. 2003; 23(4).
