Cytogenetic evidence for differences in DNA incision activity in xeroderma pigmentosum group A, C and D cells after X-irradiation during G2 phase.
The capacity of cells to incise DNA to remove altered sites after DNA damage can be determined from the rate of DNA-strand break accumulation in the presence of an inhibitor of DNA-repair synthesis, such as 1-beta-D-arabinofuranosylcytosine (ara-C). Because each chromatid contains a single continuous molecule of double-stranded DNA, chromatid breaks and gaps, i.e., non-displaced breaks, represent unrepaired DNA-strand breaks. The accumulation of chromatid breaks and gaps after X-irradiation in the presence of ara-C thus provides a measure of DNA incision activity. Addition of ara-C to skin fibroblasts or stimulated blood lymphocytes from normal individuals at intervals after X-irradiation significantly increased frequencies of chromatid breaks and/or gaps. In contrast, addition of ara-C to XP cells of complementation groups A and D had a negligible effect and a significant but less than normal effect on XP cells of complementation group C and one sample of blood lymphocytes of undetermined complementation group. The results thus show negligible incision activity after G2 phase X-irradiation in XP-A and XP-D cells and a level higher but less than normal in XP-C cells.
Parshad
R
R
Pathology Department, Howard University College of Medicine, Washington, DC 20059.
Tarone
R E
RE
Price
F M
FM
Sanford
K K
KK
D002460:Cell Line; D002842:Chromatids / Q000187:drug effects / Q000528:radiation effects; D003561:Cytarabine / Q000494:pharmacology; D004249:DNA Damage; D005347:Fibroblasts / Q000528:radiation effects; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects*; D005816:Genetic Complementation Test; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000473:pathology
D003561:Cytarabine