DNA precursor pool: a significant target for N-methyl-N-nitrosourea in C3H/10T1/2 clone 8 cells.
Synchronized C3H/10T1/2 clone 8 cells were treated in vitro with a nontoxic dose of N-methyl-N-nitrosourea during their S phase. Chromatographic isolation of the deoxyribonucleotide DNA precursor pool and measurement of the precursor content per cell showed that a nucleic acid residue in the precursor pool is 190-13,000 times more susceptible to methylation than a residue in the DNA duplex, depending on the site of methylation. This conclusion comes from measurements indicating that, for example, the N-1 position of adenine in dATP is 6.3 times more methylated than the same position in the DNA, even though the adenine content of the pool is only a fraction (0.0005) of the adenine content of the DNA helix. The comparative susceptibility between pool and DNA was found to vary with the site of methylation in the order the N-1 position of adenine greater than phosphate greater than the N-3 position of adenine greater than the O6 position of guanine greater than the N-7 position of guanine. The significance of these results for chemical mutagenesis and carcinogenesis is discussed.
D000225:Adenine / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D002999:Clone Cells / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D003854:Deoxyribonucleotides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008745:Methylation; D008770:Methylnitrosourea / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism; D013997:Time Factors
D002273:Carcinogens; D003854:Deoxyribonucleotides; D009607:Nitrosourea Compounds; D010710:Phosphates; D008770:Methylnitrosourea; D004247:DNA; D000225:Adenine