Alterations in levels of 5'-adenyl dinucleotides following DNA damage in normal human fibroblasts and fibroblasts derived from patients with xeroderma pigmentosum.
Levels of 5'-adenyl dinucleotides, measured as diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A), were found to accumulate in cultured human fibroblasts following treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the radiomimetic drug bleomycin, and nitroquinoline-1-oxide (NQO) or UV-irradiation in the presence of cytosine arabinofuranoside (araC). In contrast, cells derived from patients with xeroderma pigmentosum complementation group A (XP-A) did not demonstrate an increase in DNA-strand breaks following UV irradiation or NQO in the presence of araC nor an increase in Ap4A levels. Ap4A accumulation did occur in XP-A cells following treatment with MNNG. Cells derived from patients characterized as XP variants, which are incision repair-proficient, accumulated 5'-dinucleotides following bleomycin, MNNG and UV or NQO in the presence of araC. Taken together, these data suggest that Ap4A accumulates as a response to DNA-strand breaks.
Baker
J C
JC
Department of Biochemistry, University of California, Berkeley 94720.
Ames
B N
BN
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000032:analysis*; D001761:Bleomycin / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004249:DNA Damage; D015226:Dinucleoside Phosphates; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D003561:Cytarabine; D001761:Bleomycin; D008769:Methylnitronitrosoguanidine; C020733:diadenosine tetraphosphate; D015112:4-Nitroquinoline-1-oxide