RT Journal Article
SR Electronic
T1 DNA repair activity in protein extracts of fresh human malignant lymphoid cells.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 766
OP 771
VO 49
IS 5
A1 J M Barret
A1 P Calsou
A1 G Laurent
A1 B Salles
YR 1996
UL http://molpharm.aspetjournals.org/content/49/5/766.abstract
AB Nucleotide excision repair (NER) activity was investigated in lymphocytes from patients with chronic lymphocytic leukemia (CLL). The NER process consists of two broad stages: incision/excision of the damaged oligonucleotide and resynthesis of the repair patch. NER in CLL lymphocytes was monitored with the use of in vitro biochemical assays, allowing the determination of either the extent of repair synthesis or the incision activity on damaged plasmid DNA during incubation with whole-cell protein extracts. Fresh CLL tumor cells were purified from the blood of 7 untreated patients and 11 patients who had been treated with chemotherapy. No repair activity was found in 14 extracts (7 treated and 7 untreated) or in normal blood peripheral lymphocytes. The defect was at the level of both repair synthesis and incision/excision activity of DNA damage. In contrast, 4 of the extracts exhibited 25-60% of the repair activity measured in an extract from a control repair-proficient cell line. A linear relationship was found between the values of DNA-repair synthesis and incision activities, which indicates that the extent of significant incision was the limiting factor in these protein extracts. All of the extracts that exhibited DNA-repair activity were purified from lymphocytes of treated patients. These data suggest that chemotherapy might exert an effect on the status of repair activity in the lymphoid tumor cells of patients.