The rates of appearance and removal of 7-methylguanine and O6-methylguanine in DNA from rat liver, kidney, and colon were determined at various intervals up to 120 hr after i.p. administration of 10.2, 40.7, 81.5, or 163 mg 1,2-dimethylhydrazine (SDMH) per kg body weight (one-sixteenth, one-fourth, one-half, or one 50% lethal dose) using high-pressure liquid chromatography and fluorescence spec...

background: high-grade astrocytoma (grade 4) or glioblastoma multiforme (gbm) are deadly brain tumors. new therapies attempt to increase lifetime and quality of life in patients with malignant astrocytoma. o6-methylguanine-dna methyltransferase (mgmt) enzyme expression may be effective in prognosis and response to treatment of these patients. the aim of this study was assessment of mgmt enzyme ...

The DNA repair enzyme O6-alkylguanine DNA-alkyltransferase (OGAT) and a deficient mismatch repair system play a critical role in the resistance to chemotherapeutic agents that generate adducts at the O6-position of guanine. However, DNA adducts different from O6-methylguanine might be also involved in cytotoxicity induced by methylating agents. Because the loss of p53 function is generally asso...

Exposure of HeLa cells to 0.2 mM O6-methylguanine for 4 h or longer led to a 70-80% loss in the activity of the DNA-repair protein, O6-alkylguanine-DNA alkyltransferase. The decline in alkyltransferase activity brought about by O6-methylguanine was reversible on removing the base but at least 48 h were required for complete restoration. This loss of activity could also be brought about by other...

1. Microsomal and soluble RNA of rat liver have been studied by column and paper chromatography after administration of [Me-(14)C]methionine; evidence was obtained for the occurrence of 7-methylguanine, the methyl group being derived from methionine. 2. No evidence was obtained for the occurrence of 7-methylguanine in DNA.

The carcinogenicity of N-nitroso-N-methylurea (NMU) and Nnitroso-N-ethylurea (NEU) has been determined in adult male Syrian golden hamsters following a single i.p. injection or twothirds of the acute 50% lethal dose, or 30 and 60 mg/kg, respectively. The principal site of action of these agents was the forestomach, squamous cell papillomas of this organ developing in 53 and 61% of the animals r...

Glioblastoma multiforme (GBM) is the most common and malignant type of brain cancer. Current standard therapy for GBM involves surgery followed by ionizing radiation treatment with temozolomide (TMZ), a DNA-alkylating agent. At molecular level, TMZ produces several distinct DNA lesions such as N7 -methylguanine, N3 -methyladenine, O6 -methylguanine that all produce cytostatic cytotoxic effects ...

tion of 1-methylguanine 3-oxide was not observed (8). This observation, combined with the very low activity of 1-meth ylguanine 3-oxide as a substrate for sulfotransferase in an in vitro assay for activation (10), caused us to compare the metabolic fates of 1-methylguanine 3-oxide and 3-hydroxy 1-methylxanthine with their unmethylated parent 3-hydroxy purines to provide a better understanding o...

Endonuclease II (deoxyribonucleate oligonucleotidohydrolase, EC 3.1.4.30) of Escherichia coli has been shown to break phosphodiester bonds in alkylated DNA and depurinated DNA. The hypothesis that depurination is a step in the mechanism of the reaction with alkylated DNA is supported by in vitro experiments with DNA reacted with N-methyl-N-nitrosourea. Endonuclease II releases O(6)-methylguanin...