DNA-strand breaks associated with halogenated pyrimidine incorporation.
The alkaline elution of bromodeoxyuridine-containing (BrdUrd) DNA and chlorodeoxyuridine-containing ( CldUrd ) DNA was studied in two CHO lines, the parental AA8 and a mutant line, EM9 , which has a defect in repairing strand breaks and a 12-fold elevated baseline frequency of SCE. BrdUrd-DNA was found to have alkali-labile sites as well as direct breaks, neither of which were increased significantly by prior treatment of AA8 cells with an inhibitor (benzamide) or poly(adenosine diphosphoribose) polymerase. CldUrd -DNA, which gives higher frequencies of SCEs than BrdUrd-DNA, had more strand breaks than BrdUrd-DNA in AA8 cells after treatment with benzamide, while without benzamide there was no difference. The accumulation of breaks in CldUrd -DNA by benzamide was shown to occur rapidly, to reach a maximum by 90 min, and to be readily reversible after benzamide removal. Under all conditions, EM9 cells had more strand breaks than AA8 . These observed differences in strand breaks were not due to differences in incorporation efficiencies. For the different halogenated pyrimidines and cell types, there was a good correlation between the number of strand breaks and reduction in plating efficiencies.
D000818:Animals; D001549:Benzamides / Q000633:toxicity; D001973:Bromodeoxyuridine / Q000378:metabolism / Q000633:toxicity*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects*; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D005260:Female; D007700:Kinetics; D009154:Mutation; D010053:Ovary; D012854:Sister Chromatid Exchange / Q000187:drug effects
D001549:Benzamides; C037291:2'-chloro-2'-deoxyuridine; C037689:benzamide; D001973:Bromodeoxyuridine; D003857:Deoxyuridine