Cell extracts from Micrococcus luteus release both free 3-methyladenine and free 7-methylguanine from alkylated DNA. The glycosylase activity responsible for the liberation of 7-methylguanine is not 3-methyladenine-DNA glycosylase, which, when purified, does not liberate it. Furthermore, the heat inactivation rates of the two enzymatic activities are different. The release of 7-methylguanine by...

Ten normally occurring methylated trace bases of cytoplasmic RNA extracted from P815 ascites cells were identified as thymine, 3-methylcytosine, 5-methylcytosine, jV2-methylguanine, JV2, A^-dimethylguanine, 1-methylguanine, 7-methylguanine, 1-methyladenine, 6-methyladenine, and jV*,yV6-dimethyladenine. When the carcinostatic drug, l-methyl-2-(p-isopropylcarbamoyl)benzylhydrazine hydrochloride (...

Dimethylnitrosamine administration led to the produc tion of abnormal methylated purines in rat liver DNA. All of the methylated purines formed were lost from DNA to some extent over a 24-hr period although the rate of removal varied with the purine considered. The rates of loss of 1-methyladenine, 3-methyladenine, 7-methyladenine, 3-methylguanine, and 7-methylguanine were not changed significa...

The syntheses of novel tricyclic pyrrolo[2,3-d]pyrimidine analogues of S6-methylthioguanine are described. The crystal structures and pKa values of these and related O6-methylguanine analogues are reported. All compounds display higher pKa values than O6-methylguanine with the sulfur-containing analogues being the more basic and exhibiting higher stability in aqueous solution. In a standard sub...

The capacity to repair O6-methylguanine-DNA adducts was measured in the liver of transgenic mice expressing a chimeric gene consisting of the inducible P-enolpyruvate carboxykinase (GTP) promoter linked to the bacterial O6-alkylguanine-DNA alkyltransferase (ada) gene. Under induced conditions, total hepatic alkyltransferase reached 32.8 +/- 4.2 (SE) fmol/micrograms DNA compared to 7.8 +/- 1.1 f...

Methylhydrazine oxidation promoted by horseradish peroxidase-H2O2 or ferricyanide led to the generation of high yields of methyl radicals and to the formation of 7-methylguanine and 8-methylguanine upon interaction with calf thymus DNA. Methyl radicals were identified by spin-trapping experiments with alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone and tert-nitrosobutane. The methylated guanine ...

Repeated administration of dimethylnitrosamine (DMN) (2 mg/kg for 3 weeks) to BD IV rats results in an increased capacity for the liver to repair O6-methylguanine in DNA, whereas other DNA adducts (7-methylguanine and 3-methyladenine) are not affected. In the experiments reported here, data on the rapidity of action of the enhanced system, its capacity after different challenging doses of [14C]...

A number of methylated purine bases have recently been reported to occur in small quantities in the urine of normal human subjects. These include 1-methylguanine, iV*-methylguanine (6-hydroxy-2-methylaminopurine) ,I 1-methylhypoxanthine, and 8-hydroxy-7-methylguanine (1) in addition to 7-methylguanine, previously known as a urinary constituent (2). These compounds were found to be metabolites o...

A number of methylated purine bases have recently been reported to occur in small quantities in the urine of normal human subjects. These include 1-methylguanine, iV*-methylguanine (6-hydroxy-2-methylaminopurine) ,I 1-methylhypoxanthine, and 8-hydroxy-7-methylguanine (1) in addition to 7-methylguanine, previously known as a urinary constituent (2). These compounds were found to be metabolites o...

The ability of 7-methylguanine, a nucleic acid metabolite, to inhibit poly(ADP-ribose)polymerase-1 (PARP-1) and poly(ADP-ribose)polymerase-2 (PARP-2) has been identified in silico and studied experimentally. The amino group at position 2 and the methyl group at position 7 were shown to be important substituents for the efficient binding of purine derivatives to PARPs. The activity of both teste...