Identification of C8-methylguanine in the hydrolysates of DNA from rats administered 1,2-dimethylhydrazine. Evidence for in vivo DNA alkylation by methyl radicals

Luis E S Netto, N. V S RamaKrishna, Carol Kolar, Ercole Cavalieri, Eleanor G Rogan, Terence A. Lawson, Ohara Augusto

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

C8-Methylguanine was identified in the neutral hydrolysates of DNA isolated from the liver or colon tissue of rats administered 1,2- dimethylhydrazine. In all the samples examined, the biologically isolated adducts were characterized by co-elution with synthetic C8-methylguanine under different high pressure liquid chromatography conditions. The sample isolated from liver DNA was also identified by UV spectroscopy at different pH values and by mass spectrometry. The estimated yields of C8-methylguanine obtained in hydrolysates of DNA from the liver or colon tissue were comparable to those of O6-methylguanine. C8-Methylguanine was not detected when the spin trap α-(4-pyridyl-1-oxide)-N-tert-butylnitrone was administered together with 1,2-dimethylhydrazine. The spin trap also inhibited N7-methylguanine and O6-methylguanine yields, although to a lesser extent. These results constitute the first evidence that DNA alkylation by carbon-centered radicals can occur in vivo.

Original languageEnglish (US)
Pages (from-to)21524-21527
Number of pages4
JournalJournal of Biological Chemistry
Volume267
Issue number30
StatePublished - Jan 1 1992

Fingerprint

1,2-Dimethylhydrazine
Alkylation
Rats
Liver
DNA
Colon
High pressure liquid chromatography
Tissue
Ultraviolet spectroscopy
Oxides
Mass spectrometry
Mass Spectrometry
Spectrum Analysis
Carbon
High Pressure Liquid Chromatography
methyl radical
O-(6)-methylguanine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Identification of C8-methylguanine in the hydrolysates of DNA from rats administered 1,2-dimethylhydrazine. Evidence for in vivo DNA alkylation by methyl radicals. / Netto, Luis E S; RamaKrishna, N. V S; Kolar, Carol; Cavalieri, Ercole; Rogan, Eleanor G; Lawson, Terence A.; Augusto, Ohara.

In: Journal of Biological Chemistry, Vol. 267, No. 30, 01.01.1992, p. 21524-21527.

Research output: Contribution to journalArticle

@article{993cd2128e9146b2aa5cbaeb5efa3a25,
title = "Identification of C8-methylguanine in the hydrolysates of DNA from rats administered 1,2-dimethylhydrazine. Evidence for in vivo DNA alkylation by methyl radicals",
abstract = "C8-Methylguanine was identified in the neutral hydrolysates of DNA isolated from the liver or colon tissue of rats administered 1,2- dimethylhydrazine. In all the samples examined, the biologically isolated adducts were characterized by co-elution with synthetic C8-methylguanine under different high pressure liquid chromatography conditions. The sample isolated from liver DNA was also identified by UV spectroscopy at different pH values and by mass spectrometry. The estimated yields of C8-methylguanine obtained in hydrolysates of DNA from the liver or colon tissue were comparable to those of O6-methylguanine. C8-Methylguanine was not detected when the spin trap α-(4-pyridyl-1-oxide)-N-tert-butylnitrone was administered together with 1,2-dimethylhydrazine. The spin trap also inhibited N7-methylguanine and O6-methylguanine yields, although to a lesser extent. These results constitute the first evidence that DNA alkylation by carbon-centered radicals can occur in vivo.",
author = "Netto, {Luis E S} and RamaKrishna, {N. V S} and Carol Kolar and Ercole Cavalieri and Rogan, {Eleanor G} and Lawson, {Terence A.} and Ohara Augusto",
year = "1992",
month = "1",
day = "1",
language = "English (US)",
volume = "267",
pages = "21524--21527",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "30",

}

TY - JOUR

T1 - Identification of C8-methylguanine in the hydrolysates of DNA from rats administered 1,2-dimethylhydrazine. Evidence for in vivo DNA alkylation by methyl radicals

AU - Netto, Luis E S

AU - RamaKrishna, N. V S

AU - Kolar, Carol

AU - Cavalieri, Ercole

AU - Rogan, Eleanor G

AU - Lawson, Terence A.

AU - Augusto, Ohara

PY - 1992/1/1

Y1 - 1992/1/1

N2 - C8-Methylguanine was identified in the neutral hydrolysates of DNA isolated from the liver or colon tissue of rats administered 1,2- dimethylhydrazine. In all the samples examined, the biologically isolated adducts were characterized by co-elution with synthetic C8-methylguanine under different high pressure liquid chromatography conditions. The sample isolated from liver DNA was also identified by UV spectroscopy at different pH values and by mass spectrometry. The estimated yields of C8-methylguanine obtained in hydrolysates of DNA from the liver or colon tissue were comparable to those of O6-methylguanine. C8-Methylguanine was not detected when the spin trap α-(4-pyridyl-1-oxide)-N-tert-butylnitrone was administered together with 1,2-dimethylhydrazine. The spin trap also inhibited N7-methylguanine and O6-methylguanine yields, although to a lesser extent. These results constitute the first evidence that DNA alkylation by carbon-centered radicals can occur in vivo.

AB - C8-Methylguanine was identified in the neutral hydrolysates of DNA isolated from the liver or colon tissue of rats administered 1,2- dimethylhydrazine. In all the samples examined, the biologically isolated adducts were characterized by co-elution with synthetic C8-methylguanine under different high pressure liquid chromatography conditions. The sample isolated from liver DNA was also identified by UV spectroscopy at different pH values and by mass spectrometry. The estimated yields of C8-methylguanine obtained in hydrolysates of DNA from the liver or colon tissue were comparable to those of O6-methylguanine. C8-Methylguanine was not detected when the spin trap α-(4-pyridyl-1-oxide)-N-tert-butylnitrone was administered together with 1,2-dimethylhydrazine. The spin trap also inhibited N7-methylguanine and O6-methylguanine yields, although to a lesser extent. These results constitute the first evidence that DNA alkylation by carbon-centered radicals can occur in vivo.

UR - http://www.scopus.com/inward/record.url?scp=0026612456&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026612456&partnerID=8YFLogxK

M3 - Article

C2 - 1400464

AN - SCOPUS:0026612456

VL - 267

SP - 21524

EP - 21527

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 30

ER -