Nitrous acid mutagenesis of duplex DNA as a three-component system

Harvey F. Thomas, Philip E. Hartman, Maria Mudryj, Diane L. Brown

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purified native Hemophilus influenzae DNA is relatively insusceptible to nitrous acid (NA) mutagenesis in vitro, but is readily mutated following denaturation. NA mutagenicity for duplex DNA is significantly increased in the presence of various alcohols, glycols, phenols or primary amines. Phenolextracted DNA contains dissociable contaminants of low molecular weight that enhance NA mutagenesis. Enhancement of NA mutagenesis by phenol and by spermine is due to the formation of unstable molecular species. We propose that reactive organic nitroso compounds are formed which then serve as delivery vehicles to promote mutagenicity of native DNA, perhaps via transnitrosation reactions. Similar reactions probably occur in vivo to promote NA-induced base substitution (but not frameshift) mutations in Salmonella typhimurium and in Escherichia coli. The possible significance of these observations to carcinogenesis is discussed.

Original languageEnglish (US)
Pages (from-to)129-151
Number of pages23
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume61
Issue number2
DOIs
StatePublished - 1979
Externally publishedYes

Fingerprint

Nitrous Acid
Mutagenesis
DNA
Nitroso Compounds
Frameshift Mutation
Glycols
Spermine
Phenols
Haemophilus influenzae
Salmonella typhimurium
Phenol
Amines
Carcinogenesis
Molecular Weight
Alcohols
Escherichia coli

ASJC Scopus subject areas

  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

Nitrous acid mutagenesis of duplex DNA as a three-component system. / Thomas, Harvey F.; Hartman, Philip E.; Mudryj, Maria; Brown, Diane L.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 61, No. 2, 1979, p. 129-151.

Research output: Contribution to journalArticle

Thomas, Harvey F. ; Hartman, Philip E. ; Mudryj, Maria ; Brown, Diane L. / Nitrous acid mutagenesis of duplex DNA as a three-component system. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 1979 ; Vol. 61, No. 2. pp. 129-151.
@article{9dc916388dcb4347ad13063b50168fdc,
title = "Nitrous acid mutagenesis of duplex DNA as a three-component system",
abstract = "Purified native Hemophilus influenzae DNA is relatively insusceptible to nitrous acid (NA) mutagenesis in vitro, but is readily mutated following denaturation. NA mutagenicity for duplex DNA is significantly increased in the presence of various alcohols, glycols, phenols or primary amines. Phenolextracted DNA contains dissociable contaminants of low molecular weight that enhance NA mutagenesis. Enhancement of NA mutagenesis by phenol and by spermine is due to the formation of unstable molecular species. We propose that reactive organic nitroso compounds are formed which then serve as delivery vehicles to promote mutagenicity of native DNA, perhaps via transnitrosation reactions. Similar reactions probably occur in vivo to promote NA-induced base substitution (but not frameshift) mutations in Salmonella typhimurium and in Escherichia coli. The possible significance of these observations to carcinogenesis is discussed.",
author = "Thomas, {Harvey F.} and Hartman, {Philip E.} and Maria Mudryj and Brown, {Diane L.}",
year = "1979",
doi = "10.1016/0027-5107(79)90121-0",
language = "English (US)",
volume = "61",
pages = "129--151",
journal = "Mutation Research",
issn = "0027-5107",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Nitrous acid mutagenesis of duplex DNA as a three-component system

AU - Thomas, Harvey F.

AU - Hartman, Philip E.

AU - Mudryj, Maria

AU - Brown, Diane L.

PY - 1979

Y1 - 1979

N2 - Purified native Hemophilus influenzae DNA is relatively insusceptible to nitrous acid (NA) mutagenesis in vitro, but is readily mutated following denaturation. NA mutagenicity for duplex DNA is significantly increased in the presence of various alcohols, glycols, phenols or primary amines. Phenolextracted DNA contains dissociable contaminants of low molecular weight that enhance NA mutagenesis. Enhancement of NA mutagenesis by phenol and by spermine is due to the formation of unstable molecular species. We propose that reactive organic nitroso compounds are formed which then serve as delivery vehicles to promote mutagenicity of native DNA, perhaps via transnitrosation reactions. Similar reactions probably occur in vivo to promote NA-induced base substitution (but not frameshift) mutations in Salmonella typhimurium and in Escherichia coli. The possible significance of these observations to carcinogenesis is discussed.

AB - Purified native Hemophilus influenzae DNA is relatively insusceptible to nitrous acid (NA) mutagenesis in vitro, but is readily mutated following denaturation. NA mutagenicity for duplex DNA is significantly increased in the presence of various alcohols, glycols, phenols or primary amines. Phenolextracted DNA contains dissociable contaminants of low molecular weight that enhance NA mutagenesis. Enhancement of NA mutagenesis by phenol and by spermine is due to the formation of unstable molecular species. We propose that reactive organic nitroso compounds are formed which then serve as delivery vehicles to promote mutagenicity of native DNA, perhaps via transnitrosation reactions. Similar reactions probably occur in vivo to promote NA-induced base substitution (but not frameshift) mutations in Salmonella typhimurium and in Escherichia coli. The possible significance of these observations to carcinogenesis is discussed.

UR - http://www.scopus.com/inward/record.url?scp=0018356396&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018356396&partnerID=8YFLogxK

U2 - 10.1016/0027-5107(79)90121-0

DO - 10.1016/0027-5107(79)90121-0

M3 - Article

C2 - 314585

AN - SCOPUS:0018356396

VL - 61

SP - 129

EP - 151

JO - Mutation Research

JF - Mutation Research

SN - 0027-5107

IS - 2

ER -