Guanine-specific DNA repair after treatment of mouse skin cells with N-methyl-N'-nitro-N-nitrosoguanidine.
The incorporation of [3H]thymidine and [3H]deoxyguanosine into DNA was studied during DNA repair in mouse skin cells treated with the skin tumor initiator N-methyl-N'-nitro-N-nitrosoganidine. At high, toxic levels of N-methyl-N'-nitro-N-nitrosoguanidine, repair (incorporation of the precursor into DNA which had not replicated) was demonstrated with both precursors. At lower, less toxic doses of the carcinogen, repair could not be demonstrated with [3H]-thymidine, but it was clearly demonstrable with [3H]deoxyguanosine. Thus, we are apparently observing two kinds of DNA repair, one in which a single base (in this case, guanine) replaces a base lost by chemical or enzymatic depurination and the second in which more than one base is replaced, indicating synthesis of longer stretches DNA after extensive enzymatic excision. The guanine-specific repair shown at relatively nontoxic dose levels of N-methyl-N'-nitro-N-nitrosouanidine may be more relevant to the survival of cells than the repair demonstrated with [3H]thymidine at higher doses.
D000818:Animals; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism; D006147:Guanine / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D009604:Nitrosoguanidines / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
D004277:DNA, Single-Stranded; D006150:Guanine Nucleotides; D009604:Nitrosoguanidines; D008769:Methylnitronitrosoguanidine; D006147:Guanine; D013936:Thymidine