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.