Induction and disappearance of DNA strand breaks and/or alkali-labile sites in human lymphocytes exposed to N-ethyl-N-nitrosourea.
We investigated the induction and disappearance of DNA lesions that are detected as single-strand breaks (SSBs) with the alkaline filter elution technique, in human peripheral blood lymphocytes (PBLs) following exposure to N-ethyl-N-nitrosourea (ENU). In PBLs of the 15 individuals studied, 35 +/- 16% (mean +/- SD) of the SSBs present at the end of a 20 min treatment disappeared within 1 h; up to 24 h post-treatment no further disappearance was observed. Interindividual differences in SSB disappearance were considerable; in two cases, almost no SSBs disappeared over the 1 h period. In PBLs of the same 15 individuals 85 +/- 3% (mean +/- SD) of the SSBs induced by 4 Gy of gamma-rays were found to disappear within 1 h, which indicated no interindividual differences. Multiple blood sampling at 1 month intervals indicated that interindividual differences in ENU-induced SSB repair are constant and do not vary with time. The low rate of SSB disappearance appeared to correlate with low cell survival after ENU exposure, measured as a reduction in phytohemagglutinin-stimulated incorporation of [3H]-thymidine. The cytosine analog 1-beta-D-arabinofuranosyl-cytosine completely inhibited SSB disappearance, indicating that the removal of the repairable ENU-induced SSBs involves excision repair events.
Boerrigter
M E
ME
Department of Molecular Biology, TNO Institute for Experimental Gerontology, The Netherlands.
Mullaart
E
E
Berends
F
F
Vijg
J
J
D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000187:drug effects*; D005038:Ethylnitrosourea / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*
D004277:DNA, Single-Stranded; D003561:Cytarabine; D005038:Ethylnitrosourea