DNA repair in xeroderma pigmentosum cells treated with combinations of ultraviolet radiation and N-acetoxy-2-acetylaminofluorene.
We used three techniques to examine excision repair in human cells treated with ultraviolet radiation, N-acetoxy-2-acetylaminofluorene, and a combination of the two. The three techniques gave similar results. Two types of human cells were used: (a) excision repair proficient (normal human fibroblasts and xeroderma pigmentosum variants); and (b) excision repair deficient (xeroderma pigmentosum C, D, and E). Saturation doses were determined and used for combined treatments with both agents. We observed two patterns of repair: (a) in repair-proficient cells total repair was additive; and (b) in repair-deficient cells total repair was much less than additive (usually less than that repair was much less than additive (usually less than that observed for separate treatments) and N-acetoxy-2-acetylaminofluorene inhibited excision of pyrimidine dimers. We conclude that, in the first group of cells, pathways for repair of ultraviolet radiation- and N-acetoxy-2-acetylaminofluorene-induced lesions are not identical and, in the second group of cells, there is an inhibitory effect exerted by major or minor products of each agent on the repair enzyme(s) of the other.
D000099:Acetoxyacetylaminofluorene / Q000494:pharmacology*; D001973:Bromodeoxyuridine; D002460:Cell Line; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004720:Endonucleases / Q000494:pharmacology; D005449:Fluorenes / Q000494:pharmacology*; D009374:Neoplasms, Experimental / Q000378:metabolism; D010782:Photolysis; D011740:Pyrimidine Dimers / Q000378:metabolism; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000378:metabolism*
D004273:DNA, Neoplasm; D005449:Fluorenes; D011740:Pyrimidine Dimers; D000099:Acetoxyacetylaminofluorene; D004720:Endonucleases; D001973:Bromodeoxyuridine