Source of Urinary 8-Hydroxy-7-methylguanine in Man<sup>*</sup>

Litwack, Marcia; Weissmann, Bernard

doi:10.1021/bi00873a033

Cited by 16 publications

(5 citation statements)

References 25 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and mass spectra as 1-, N2-, 3-, 06 , 7-and 9-ethylguanine (Tables 1 and 3). The results may be compared with those found by Litwack & Weissmann (1966) on methylation of guanine, where alkylation at the 1-, N2-, 7-and 9-positions was observed.…”

Section: Resultsmentioning

confidence: 77%

Isolation and identification of products from alkylation of nucleic acids: ethyl- and isopropyl-purines

Lawley¹,

Orr²,

Jarman³

1975

Biochemical Journal

106

View full text Add to dashboard Cite

Ethylation and isopropylation of guanine in alkaline solution, or of adenine in formic acid, by alkyl methanesulphonates gave the following products: 1-, N2-, 3-, O6-, 7- and 9-alkylguanines; 1-, 3-, 7- and 9-alkyladenines. The products were identified from their characteristic u.v-absorption spectra, by comparison with either known ethyladenines or with the corresponding known methyladenines, and were also characterized by mass spectrometry. Their chromatographic properties on paper, t.l.c. and various columns were determined. DNA was alkylated in neutral solution with 14C-labelled alkyl methanesulphonates and the ratios of the alkylpurines formed were obtained, and compared for alkylation by methyl, ethyl and isopropyl methanesulphonates and by N-methyl-N-nitrosourea. The extents of alkylation at O-6 of guanine relative to those at N-7 of guanine varied with the reactivity of the methylating agents according to the predictions of Swain & Scott (1953) relating nucleophilicity of the groups alkylated with the substrate constants of the alkylating agents. The relative extents of alkylation at N-3 of adenine did not follow this correlation.

show abstract

Section: Resultsmentioning

confidence: 77%

Isolation and identification of products from alkylation of nucleic acids: ethyl- and isopropyl-purines

Lawley¹,

Orr²,

Jarman³

1975

Biochemical Journal

106

View full text Add to dashboard Cite

show abstract

“…(1956) and purified by chromatography in solvent II followed by solvent III. 3-Ethylguanine was prepared in low yield by a modification of the method of Litwack and Weissmann (1966) for the preparation of methylguanines. Ethyl chloride was the alkylating agent and 3-ethylguanine was separated from all other ethylguanines (including 7, 9, and 1,7 derivatives) by chromatography in solvents I and II.…”

Section: Methodsmentioning

confidence: 99%

Specificity of different classes of ethylating agents toward various sites in RNA

TSinger¹,

Fraenkel‐Conrat²

1975

Biochemistry

View full text Add to dashboard Cite

The alkyl products of neutral in vitro ethylation of TMV-RNA by [14C]diethyl sulfate, [14C]ethyl methanesulfonate, and [14C]ethylnitrosourea have been determined and found to differ significantly depending on the ethylating agent. Diethyl sulfate and ethyl methanesulfonate ethylate the bases of TMV-RNA in the following order: 7-ethylguanine greater than 1-ethyladenine, 3-ethylcytidine greater than 7-ethyladenine, 3-ethyladenine, O6-ethylguanosine, 3-ethylguanine. Ethyl methanesulfonate was more specific for the 7 position of guanine, and other derivatives were found in lesser amounts than with diethyl sulfate. Neither reagent caused the formation of detectable amounts (smaller than 0.26 percent) of 1-ethylguanine, 1,7-diethylguanine, N2-ethylguanine, N6-ethyladenine, N4-ethylcytidine, or 3-ethyluridine. Identified ethyl bases account for over 85% of the total radioactivity of [14C]ethyl methanesulfonate and [14C]diethyl sulfate treated TMV-RNA. Phosphate alkylation accounts for about 13 and 1%, respectively, In contrast, [14C]ethylnitrosourea-treated TMV-RNA, while reacting to a similar extent (15-70 ethyl groups/6400 nucleotides), is found to cause considerably more phosphate alkylation. Upon either U4A RNase or acid hydrolysis up to 60% of the radioactivity is found as volatile ethyl groupw in the form of [14C]ethanol, and a further 15% appears to be primarily ethyl phosphate and nucleosides with ethylated phosphate. Of the remaining radioactivity, half is found as O6-ethylguanosine, the major identified ethyl nucleoside. Other ethyl bases found in ethylnitrosourea-treated TMV-RNA are 7-ethylguanine greater than 1-ethyladenine, 3-ethyladenine, 7-ethyladenine, 3-ethylcytidine, and 3-ethylguanine. It appears that ethylnitrosourea preferentially alkylates oxygens, and that formation of phosphotriesters is by far the predominant chemical event. Since the number of ethyl groups introduced into TMV-RNA by ethylnitrosourea is similar to the number of lethal events, one may conclude that phosphate alkylation leads to loss of infectivity. None of the three ethylating agents studied are strongly mutagenic on TMV-RNA or TMV. The role of phosphate alkylation in regard to in vivo mutagenesis and oncogenesis remains to be established. At present it appears possible that the extent of this reaction may correlate better with the oncogenic effectiveness of different ethylating agents, than the extent of any base reaction. Unfractionated HeLa cell RNA is ethylated primarily in acid labile manner even by diethyl sulfate and ethyl methanesulfonate, a fact that is attributed to its high content of low molecular weight trna rich in terminal phosphates which alkylate readily.

show abstract

“…Reported instances of chemical alkylation at the extranuclear N atom of guanine are few. Litwack & Weissmann (1966) described N2-methylguanine among the products of methylation of guanine with methyl chloride in aqueous ethanolic NaOH. According to Dipple et al (1971) the extranuclear amino group was the principal site of alkylation of guanine in 2'-deoxyguanosine and in DNA by 7-bromomethylbenz[a]anthracene in aqueous solution.…”

Section: Hydrolysis Of Methyl and Ethyl Derivatives Of 2'deoxyguanosinementioning

confidence: 99%

The alkylation of 2′-deoxyguanosine and of thymidine with diazoalkanes. Some observations on O-alkylation

Farmer

Foster

Jarman

et al. 1973

Biochemical Journal

View full text Add to dashboard Cite

The reaction in ether-methanol between 2'-deoxyguanosine and diazomethane or its ethyl or n-butyl homologue gives 1-, O(6)- and 7-alkyl-2'-deoxyguanosine. N(2),O(6)-Dimethyl-2'-deoxyguanosine was also detected. The hydrolysis of the methyl and the ethyl derivatives gives the corresponding alkylguanines: the O(6)-alkyl-2'-deoxyguanosines were sequentially hydrolysed, first to 2-amino-6-alkoxypurines, subsequently to guanine. The mass spectra of O(6)-alkyl-2'-deoxyguanosines (methyl and ethyl) and of the corresponding 2-amino-6-alkoxypurines were determined. The reaction of diazomethane with thymidine afforded O(4)-methylthymidine, in addition to the previously detected 3-methylthymidine.

show abstract

Source of Urinary 8-Hydroxy-7-methylguanine in Man^*

Cited by 16 publications

References 25 publications

Isolation and identification of products from alkylation of nucleic acids: ethyl- and isopropyl-purines

Isolation and identification of products from alkylation of nucleic acids: ethyl- and isopropyl-purines

Specificity of different classes of ethylating agents toward various sites in RNA

The alkylation of 2′-deoxyguanosine and of thymidine with diazoalkanes. Some observations on O-alkylation

Contact Info

Product

Resources

About

Source of Urinary 8-Hydroxy-7-methylguanine in Man*

Cited by 16 publications

References 25 publications

Isolation and identification of products from alkylation of nucleic acids: ethyl- and isopropyl-purines

Isolation and identification of products from alkylation of nucleic acids: ethyl- and isopropyl-purines

Specificity of different classes of ethylating agents toward various sites in RNA

The alkylation of 2′-deoxyguanosine and of thymidine with diazoalkanes. Some observations on O-alkylation

Contact Info

Product

Resources

About

Source of Urinary 8-Hydroxy-7-methylguanine in Man^*