Comet-assay analysis identifies genomic damage in lymphocytes of uremic patients.
This study investigates genomic damage in peripheral lymphocytes from patients with moderate to severe chronic renal insufficiency and those on long-term maintenance hemodialysis (MHD) and hemodiafiltration therapy. As a measure for genomic damage, the comet assay (single-cell gel electrophoresis) was applied. This test detects single- and double-strand breaks and alkali labile sites through electrophoretic mobility of the resulting fragments. The average damage (percentage of DNA in the tail region of the comet) observed in cells of the control group of 21 healthy subjects was 10.5% +/- 0.8%. There was a significant increase to 14.7% +/- 3.5% in cells of 23 patients with chronic renal failure, and a further increase to 17.1% +/- 3.5% in the subgroup of 12 patients with serum creatinine values greater than 6 mg/dL. Damage was 16.7% +/- 4.2% in cells of the MHD group (26 patients) and 20.1% +/- 3.0% in the subgroup with MHD therapy longer than 10 years (8 patients). Cellular DNA damage in the group of 15 maintenance hemodiafiltration patients was 15.6% +/- 2.1%, ranging between predialysis and MHD patients, and did not seem to increase with treatment time. These results, together with previously observed elevated frequencies of micronuclei, decreased DNA repair, and increased cancer incidence described for these patient groups, emphasize the need to further optimize the current therapy for reducing the degree of genomic damage.
Stopper
H
H
Departments of Toxicology and Internal Medicine, Universität Würzburg, FRG. stopper@toxi.uni-wuerzburg.de
Boullay
F
F
Heidland
A
A
Vienken
J
J
Bahner
U
U
D000328:Adult; D000368:Aged; D020552:Comet Assay; D004247:DNA / Q000032:analysis*; D004249:DNA Damage; D005260:Female; D017583:Hemodiafiltration; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics* / Q000628:therapy; D008214:Lymphocytes / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
D004247:DNA