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PMID: 1059105 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Mutagenicity of chloroacetaldehyde, a possible metabolic product of 1,2-dichloroethane (ethylene dichloride), chloroethanol (ethylene chlorohydrin), vinyl chloride, and cyclophosphamide.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 72 ·No. 8 ·1975-08-00 ·Pages 3190-3

McCann J, Simmon V, Streitwieser D, Ames BN

Abstract

We have previously described a very sensitive and efficient bacterial test designed to detect chemical carcinogens as mutagens. Chloroacetaldehyde is mutagenic in this system and is of interest because it is a possible metabolite in mammals of the large volume industrial chemicals 1,2-dichloroethane (ethylene dichloride) (3.5 billion kg/yr, U.S.) and vinyl chloride (2.5 billion kg/yr, U.S.), and of the antineoplastic agent cyclophosphamide. Chloroacetaldehyde reverts a new Salmonella bacterial tester strain (TA100). Chloroacetaldehyde is shown to be hundreds of times more effective in reversion of TA100 than is chloroethanol (ethylene chlorohydrin), a known metabolic precursor of chloroacetaldehyde and a possible metabolite of dichloroethane and vinyl chloride, or than vinyl chloride, which is itself mutagenic for TA100. Chloroethanol is shown to be activated by rat (or human) liver homogenates to a more highly mutagenic form with reversion properties similar to chloroacetaldehyde. Reversion properties of cyclophosphamide after in vitro metabolic activation suggest that chloroacetaldehyde is not the active mutagenic form of this antineoplastic drug.

MeSH Terms
Acetaldehyde/analogs & derivatives,pharmacology Chlorohydrins/metabolism Cyclophosphamide/metabolism Ethylene Chlorohydrin/metabolism Ethylene Dichlorides/metabolism Hydrocarbons, Chlorinated/metabolism Mutagens Salmonella/drug effects Vinyl Chloride/metabolism Vinyl Compounds/metabolism
Chemicals
Chlorohydrins Ethylene Dichlorides Hydrocarbons, Chlorinated Mutagens Vinyl Compounds Ethylene Chlorohydrin Cyclophosphamide Acetaldehyde Vinyl Chloride
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
McCann J
Simmon V
Streitwieser D
Ames B N
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35 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.72.8.3190
Published
1975-08-00
Pages
3190-3
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC432947
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.72.8.3190 PMC Full Text View journal details
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