methylnitronitrosoguanidine and 3-methyladenine

Escherichia coli alkB mutants are sensitive to methyl methanesulfonate and dimethylsulphate, and are defective in the processing of methylated DNA. The function of the AlkB protein has not been determined. Here, we show that alkB mutants are not defective in repairing several different types of potentially toxic DNA lesions that are known to be generated by MMS, including apyrimidinic and apurinic sites, and secondary lesions that could arise at these sites (DNA-protein cross-links and DNA interstrand cross-links). Also, alkB mutants were not sensitive to MeOSO2-(CH2)2-Lex, a compound that alkylates the minor groove of DNA generating primarily 3-methyladenine.

Topics: Adenine; Apurinic Acid; Bacterial Proteins; Bacteriophage lambda; Binding Sites; Cytochrome P-450 CYP4A; Cytochrome P-450 Enzyme System; DNA Damage; DNA Repair; DNA, Bacterial; DNA, Viral; Escherichia coli; Escherichia coli Proteins; Indicators and Reagents; Methyl Methanesulfonate; Methylnitronitrosoguanidine; Mixed Function Oxygenases; Mutagens; Mutation; Netropsin; Polynucleotides; Sulfuric Acid Esters; Virus Replication

Mer- human cells, which lack O6-methylguanine DNA methyltransferase activity, are extremely sensitive to alkylation induced killing, mutation and sister chromatid exchange. We have analyzed a Mer+, a Mer-, and a Mer- revertant HeLa cell line and found that the methyltransferase deficiency correlates with increased levels of mutation and sister chromatid exchange, but does not correlate with increased killing of Mer- HeLa cells by alkylating agents. Furthermore, we show that HeLa Mer- cells repair N-3-methylguanine and N-3-methyladenine just as efficiently as HeLa Mer+ cells.

Topics: Adenine; Alkylating Agents; Alkylation; Cell Survival; DNA Repair; Guanine; HeLa Cells; Humans; Methylnitronitrosoguanidine; Purines; Sister Chromatid Exchange

We have isolated and characterized a mutant of baker's yeast, Saccharomyces cerevisiae, carrying the new mutation, ngs1, which is sensitive to the toxic effects of monofunctional alkylating agents, but normal with respect to 254-nm ultraviolet light sensitivity. ngs1 mutants exhibited more or less normal reversion frequencies for his1-7 and ilv1-92 induced by each of these mutagens. The various sensitivities associated with ngs1 cosegregated and have been shown to be the result of a lesion in a single nuclear gene. Extracts of ngs1 and NGS1+ strains contained approximately equal levels of an activity that removes 3-methyladenine (3MA) and 7-methylguanine (7MG) from DNA in vitro. The mutation also depressed sporulation.

Topics: Adenine; Alkylating Agents; DNA Repair; Genes, Fungal; Guanine; Methylnitronitrosoguanidine; Mutation; Saccharomyces cerevisiae; Sulfuric Acid Esters

Two cell lines, one proficient (Mex+) and one deficient (Mex-) in the ability to remove O6-methylguanine, have been isolated by Epstein-Barr virus-mediated transformation of a single blood sample obtained from a normal human male. Extracts of untreated cells differ in their O6-methylguanine transferase (methyl acceptor protein) activity. Although both lines arise from the same individual, they show great difference in their sensitivities to the toxic action of N-methyl-N'-nitro-N-nitrosoguanidine. Chromosome counts of the strains reveal a modal number of 46 for both. Neither X-inactivation nor a gross abnormality in chromosome number can be the cause of the difference between the two lines.

Topics: Adenine; Cell Division; Cell Line; Chromosome Aberrations; Guanine; Humans; Karyotyping; Lymphocyte Activation; Lymphocytes; Male; Methylnitronitrosoguanidine

Topics: 1,2-Dimethylhydrazine; Adenine; Alkylating Agents; Animals; Carcinogens; Dimethylhydrazines; Dimethylnitrosamine; Guanine; Male; Methyl Methanesulfonate; Methylation; Methylnitronitrosoguanidine; Niacinamide; Rats