Gamma-irradiation-induced DNA single- and double-strand breaks and their repair in chronic lymphocytic leukemia cells of variable radiosensitivity.
Gamma-irradiation-induced DNA single- and double-strand break (SSB and DSB) formation and their repair kinetics in normal hematopoietic cells and in leukemic lymphocytes was investigated using alkaline and neutral comet assays. The cells were isolated by density gradient centrifugation from peripheral blood of patients with chronic lymphocytic leukemia (CLL) and from healthy study subjects. Furthermore, CD34+ progenitor cells isolated with immunomagnetic beads from bone marrow of non-leukemic persons were investigated. The cytotoxicity of 137Cs irradiation was determined in vitro in peripheral blood mononuclear lymphocytes from 36 CLL patients and from 8 healthy donors using radioactive leucine incorporation assay in 4-day culture. A dose-dependent increase in DNA migration was observed in alkaline (SSBs) and neutral (DSBs) gel electrophoresis when the cells were exposed to gamma-irradiation doses up to 10.4 Gy. After irradiation with doses of 2.4 and 5.4 Gy, the cells repaired their single- and double-strand breaks almost completely. The formation and repair of DNA strand breaks were essentially similar in all normal cell populations investigated and in CLL cells. The gamma-irradiation-induced cytotoxicity did not correlate with DNA strand break formation and repair capacity. According to these results, the differences of gamma-irradiation tolerance among individual CLL cases and among healthy persons are explicable in terms other than DNA strand break formation or repair.
Myllyperkiö
M H
MH
Department of Clinical Chemistry, University Hospital, and University of Tampere Medical School, Finland.
Koski
T R
TR
Vilpo
L M
LM
Vilpo
J A
JA
D000368:Aged; D018952:Antigens, CD34; D016923:Cell Death / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006412:Hematopoietic Stem Cells / Q000528:radiation effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000528:radiation effects; D008214:Lymphocytes / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D011836:Radiation Tolerance
D018952:Antigens, CD34; D004277:DNA, Single-Stranded; D004247:DNA