Induction and disappearance of DNA strand breaks in human peripheral blood lymphocytes and fibroblasts treated with methyl methanesulfonate.
The induction and disappearance of DNA single-strand breaks (SSB) in human peripheral blood lymphocytes (PBL) and fibroblasts exposed to methyl methanesulfonate (MMS) were investigated by using the alkaline filter elution assay. In the two cell types, identical amounts of SSB were induced during a 45-min treatment with a given dose of MMS. In quiescent PBL only 9 +/- 4% (mean +/- SD) of the induced SSB had disappeared at 1 h after exposure, whereas in phytohemagglutinin-stimulated PBL, 23 +/- 12% disappeared within the same repair period. The percentage SSB disappearance in confluent fibroblasts was 25 +/- 2% at 1 h after exposure. As in PBL, the percentage SSB disappearance in fibroblasts appeared to be proliferation-dependent; actively dividing fibroblasts removed 50 +/- 12% of the MMS-induced SSB during the 1-h repair period. The accumulation of SSB in PBL, but not in fibroblasts, during MMS exposure in the presence of the excision-repair inhibitor 1-beta-D-arabinofuranosylcytosine indicated the utilization of different repair pathways in these two cell types. The generally lower rate of disappearance of MMS-induced SSB in PBL as compared to fibroblasts correlated with an increased loss of cell viability, measured by determining the incorporation of [3H]thymidine.
Boerrigter
M E
ME
Department of Molecular Biology, TNO Institute for Experimental Gerontology, Rijswijk, The Netherlands.
Mullaart
E
E
Vijg
J
J
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000235:genetics; D003561:Cytarabine / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008741:Methyl Methanesulfonate / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology
D010835:Phytohemagglutinins; D003561:Cytarabine; D008741:Methyl Methanesulfonate