Disease relevance of NSC19647

• Di-and trimethylated congeners of 7-methylguanine in Sindbis virus mRNA [1].
• The yeast enzyme was able to excise 7-methylguanine as well as 3-methyladenine from dimethyl sulphate treated DNA, confirming the related nature of this enzyme to the AlkA DNA glycosylase from E. coli [2].
• Release of 7-methylguanine residues from alkylated DNA by extracts of Micrococcus luteus and Escherichia coli [3].
• Ratios of N7-methylguanine in BOP versus HPOP treated hamsters, at doses less than 40 mg/kg body weight, were 3.1 in the kidney, 7.0 in the pancreas, 3.9 in the lung, and only 3.5 in the liver [4].
• Neoplastic transformation has been demonstrated for a 1-methylguanine-derived line, and both 1-methylguanine- and 7-methylguanine-treated cell lines exhibit characteristics similar to those of Chinese hamster cells transformed with the carcinogen 3,4-benzopyrene or the DNA tumor virus SV40 [5].

Psychiatry related information on NSC19647

• Decreasing urinary PAH metabolites and 7-methylguanine after smoking cessation [6].

High impact information on NSC19647

• Therefore, we decided to investigate the alkylation and repair of O(6)-and 7-methylguanine in the target and non-target cells following oral administration of 1,2-dimethylhydrazine [7].
• Two hours after the end of the infusion, the amount of 7-methylguanine was highest in the G0-phase liver, with a decrease in the G1 phase, the S-phase, and the G2+M-phase [8].
• Measurements were made of the amounts of O6-methylguanine and 7-methylguanine present in liver DNA at 4 and 24 hours after treatment with the carcinogen [9].
• Crude extracts of BH290 cells harboring the pAPDG10 plasmid released 3-meAde and 7-methylguanine residues from DNA methylated with [methyl-3H]dimethylsulfate [10].
• The isozyme form of eukaryotic initiation factor 4F [eIF-(iso)4F] from wheat germ is composed of a p28 subunit that binds the 7-methylguanine cap of mRNA and a p86 subunit having unknown function [11].

Chemical compound and disease context of NSC19647

• Biological properties of imidazole ring-opened N7-methylguanine in M13mp18 phage DNA [12].
• O6-methylguanine, but not N7-methylguanine or N3-methyladenine, induces gene mutations, sister-chromatid exchanges and chromosomal aberrations in Chinese hamster cells [13].
• This adduct, which accounted for 55% of the total methyl residues in DNA at 72 hours after carcinogen treatment, was chromatographically identical to a synthetic purine ring-opened derivative of 7-methylguanine and could be released from the isolated hepatic DNA by a specific E. coli glycosylase [14].
• After oral administration of NMBzA the reaction with DNA was more extensive, in particular in the diverticulum (crop), where N7-methylguanine and 0(6)-methylguanine amounted to 32 and 3.5 mumol/mol guanine, respectively [15].
• The methylation patterns produced in E. coli B tRNA by various concentrations of dimethylsulphate were found to differ with a predominant formation of 7-methylguanine and 1-methyladenine at low concentrations and of a methylated compound not yet identified at high concentrations of methylating agent [16].

Biological context of NSC19647

• In contrast, there was no difference between the human and rat liver extracts in catalyzing the loss of another methylation product, 7-methylguanine, from alkylated DNA [17].
• As MMS produces less methylation at the O6 position of guanine and more methylation at the N7 position in comparison to MNNG, the results suggest that: (i) N7-methylguanine is not implicated in the adaptive response and (ii) adaptation to mutagenesis can be correlated with the amount of O6-methylguanine induced during the pretreatment [18].
• The cloned cDNA, expressed from the pBR322 beta-lactamase promoter, contains an 894-base-pair open reading frame encoding a 32,894-Da protein able to release 3-MeAde, but not 7-methylguanine, from alkylated DNA [19].
• A characteristic feature of gene expression in eukaryotes is the addition of a 5'-terminal 7-methylguanine cap (m7GpppN) to nascent pre-mRNAs in the nucleus catalyzed by capping enzyme and cap methyltransferase [20].
• In addition, the repair of N7-methylguanine in the overall genome was assessed by use of a 32P end-labeling technique [21].

Anatomical context of NSC19647

• The null status of the animals was confirmed at the mRNA level by reverse transcription-PCR and by the inability of cell extracts of tissues from the knockout (ko) animals to release 3-methyladenine (3-meA) or 7-methylguanine (7-meG) from 3H-methylated calf thymus DNA in vitro [22].
• Highest levels of DNA alkylation were found in esophagus (798 mumol 7-methylguanine/mol mol guanine), followed by nasal epithelium (672 mumol) and liver (624 mumol) [23].
• 7-Methylguanine was found in hydrolysates of liver and pancreas DNA from Syrian golden hamsters given a single dose of N-[1-14C]nitrosobis(2-oxopropyl)amine (BOP) [24].
• Concentrations of 7-methylguanine in liver were approximately 15 times higher than in kidney, 100 times higher than in esophagus, and 200 times higher than in lung [25].
• Among the other organs investigated (brain, lung, spleen, small intestine), 7-methylguanine levels showed little variation but were 4 to 7 times lower than those in liver and kidney [26].

Associations of NSC19647 with other chemical compounds

• Under conditions where methylation at the O6 position of guanine in double-stranded DNA was inhibited 65% by ellagic acid, no significant inhibition of either O6- or 7-methylguanine formation was detected in single-stranded DNA [27].
• Quantitation of N7-methylguanine by its UV spectrum and radioactivity, following administration of single-labeled [1-14C]BOP or HPOP, showed that the specific activity of this adduct was one half that of the nitrosamine [4].
• The RNA catabolite 7-methylguanine has been shown to inhibit queuine modification of tRNA in Chinese hamster embryo cells under conditions leading to in vitro transformation [28].
• Repair kinetics for the removal of alkali-labile sites were comparable across the entire genome in the RINr 38 and RINr B2 cells as determined using alkaline sucrose gradient sedimentation and a 32P end-labeling assay for the quantitation of N7-methylguanine [29].
• The main methylation site in DNA is 7-methylguanine and its level is higher than that found by others in the DNA of other cell types after treatment with methylnitrosourea; however, methylation of the two types of protein (especially the histones) is relatively very low [30].

Gene context of NSC19647

• Evidence is also provided that the BER intermediates resulting from excision of 7-methylguanine by wild-type AAG contributes to the mutagenicity and cytotoxicity of alkylating agents [31].
• As this mutagenic event occurs during the growth of adenomas, both biomarkers of exposure (N7-methylguanine levels in DNA) and susceptibility (MGMT activity) were measured in biopsy samples obtained from normal and adenomatous tissue from 34 patients with large adenomas (>10 mm in size) [32].
• Then, we determined DNA strand breaks and the level of 7-methylguanine (7-mGua), a product of NNK metabolism by cytochrome P450 (CYP) [33].
• We also investigated the in vivo repair kinetics of another Aag substrate, 7-methylguanine [34].
• Nuclear DNAs of tissue culture cells treated with 0, 0.01 and 0.1 mM N-methyl-N'-nitro-N-nitrosoguanidine contained 0.18, 31 and 320 mumol, respectively, of 7-methylguanine adducts per mol of nucleotides [35].

Analytical, diagnostic and therapeutic context of NSC19647

• A method for the analysis of 7-methylguanine adducts has been developed by combining the selectivity of separation of reversed-phase HPLC with the specificity and high sensitivity of electrochemical detection [36].
• The specific binding of N7-methylguanine cap analogues to the RNA methyltransferase VP39 was observed through X-ray crystallography, providing a prototypical structure for a complex between a protein and an mRNA 5' cap [37].
• Feeding of a protein-free diet prior to 3,3-[14C]dimethyl-1-phenyltriazene administration reduced the formation of 7-methylguanine in liver and kidney RNA, whereas in the remaining organs the extent of methylation was markedly increased [26].
• A 7-methylguanine (m7G) specific tRNA methyltransferase from E. coli MRE 600 was purified about 1000 fold by affinity chromatography on Sepharose bound with normal E. coli tRNA [38].
• We have used a combination of thin-layer chromatography (TLC) and high pressure liquid chromatography (HPLC) to achieve separation of 32P-postlabelled 7-methylguanine and 7-(2-hydroxyethyl)-guanine adducts [39].

References