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HERO ID
2776783
Reference Type
Journal Article
Title
Preventive Action of Thioethers Towards In Vitro DNA Binding and Mutagenesis in E. coli K12 by Alkylating Agents
Author(s)
Kroese, ED; Zeilmaker, MJ; Mohn, GR; Meerman, JHN
Year
1990
Is Peer Reviewed?
1
Journal
Mutation Research
ISSN:
0027-5107
EISSN:
1873-135X
Report Number
NIOSH/00199538
Volume
245
Issue
2
Page Numbers
67-74
Language
English
PMID
2215553
Abstract
The preventive effects of thioethers toward DNA binding and mutagenesis of alkylating agents were studied in-vitro. Cultures of Escherichia-coli strain K12 were pretreated with 20 millimolar (mM) 4-(methylthio)benzoic-acid (MTB), methionine, glutathione or cysteine. They were then incubated with 104mM radiolabeled ethylnitrosourea (759739) (ENU) or 169mM labeled ethylmethane-sulfonate (62500) (EMS). The DNA was isolated and the extent of ENU and EMS binding was determined. K12 cultures were pretreated with 20mM methyl-4-(methylthio)benzoate (MMTB), MTB, glutathione, or cysteine. They were then treated with 0 to 90mM methylnitrosourea (684935) (MNU), methylmethanesulfonate (66273) (MMS), ENU, or EMS. The cultures were tested for mutagenicity by determining the frequency of argine+ revertants. ENU and EMS alone bound to K12 DNA to similar extents, 330 and 440 picomoles per milligram, respectively. Only MTB inhibited ENU/DNA binding. Only glutathione and cysteine inhibited EMS/DNA binding. Only MTB inhibited ENU mutagenesis. Only glutathione and cysteine inhibited EMS mutagenicity. MTB, MMTB, glutathione, and cysteine inhibited MNU mutagenicity. Glutathione and MTB inhibited MMS mutagenicity. The authors conclude that aromatic thioethers can trap genotoxic electrophiles formed from ENU and MNU inhibiting their ability to bind to DNA and induce mutagenicity. Aromatic thioethers may act as anticarcinogens toward ENU and MNU.
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