Mutagenicity of vinyl chloride, chloroethyleneoxide, chloroacetaldehyde and chloroethanol

Malaveille, Christian; Bartsch, Helmut; Barbin, Alain; Camus, Anne-Marie; Montesano, Ruggero; Croisy, Alain; Jacquignon, P.

doi:10.1016/0006-291x(75)90697-x

Cited by 173 publications

(41 citation statements)

References 4 publications

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“…Fig. 1A shows that, at the levels tested, chloroacetaldehyde is quite effective in reverting TA100, but does not revert TA1535. [We find at higher concentrations a slight activity of chloroacetaldehyde in reverting TA1535; weak activity has been found independently (14)(15)(16)(17).] Chloroacetaldehyde is relatively specific for TA100, and does not significantly revert the other R factor tester strain, TA98 (TA1538 containing the pKM101 plasmid), or our other standard tester strains.…”

Section: Resultssupporting

confidence: 58%

“…Chloroacetaldehyde has also become of interest recently as a possible metabolic product of the large volume industrial chemical, and human carcinogen vinyl chloride (15)(16)(17)(22)(23)(24)(25). It is also a possible active metabolite of several widely used chemicals and we discuss this in relation to its mutagenicity.…”

Section: Resultsmentioning

confidence: 99%

“…It has been used extensively for fluorescent labeling of a variety of adenine and cytosine containing compounds, including single-stranded DNA. The mutagenic activity of chloroacetaldehyde reported here strongly suggests it can also react with chromosomal DNA, possibly at exposed singlestranded regions such as the replication fork, or in regions of the DNA undergoing recombinational repair.Chloroacetaldehyde has also become of interest recently as a possible metabolic product of the large volume industrial chemical, and human carcinogen vinyl chloride (15)(16)(17)(22)(23)(24)(25). It is also a possible active metabolite of several widely used chemicals and we discuss this in relation to its mutagenicity.…”

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confidence: 99%

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

McCann¹,

Simmon²,

Streitwieser³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

147

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We have previously described a very sensitive and efficient bacteria] 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 1,2dichloroethane (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 Salmoneira bacterial tester strain (TAlOO). 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 TAIOO. 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 jwperties of cyclophosphamide after in vitro metabolic activation suggest that chloroacetaldehyde is not the active mutagenic form of this antineoplastic drug. We have previously described a rapid, sensitive bacterial test designed to detect chemical carcinogens as mutagens (1-7). The test utilizes a special set of histidine mutants of Salmonella typhimurium for reversion, and a rat (or human) microsomal system for metabolic conversion of carcinogens to their active forms. The standard bacterial tester strains have been described in detail (1, 3, 5) and contain histidine missense (TA1535) or frameshift (TA1537, TA1538) mutations. The strains also contain uvrB and rfa (deep rough) mutations which greatly increase their sensitivity to reversion by a variety of carcinogens: uvrB causes loss of the excision repair system and rfa causes loss of the lipopolysaccharide permeability barrier. The compound to be tested, the bacterial tester strain, and when required rat (or human) liver microsomal enzymes, are combined on a petri dish and after incubation at 370 for 2 days histidine revertants are scored.Hundreds of carcinogens and noncarcinogens have been tested using the Salmonella/mammalian-microsome bacterial test system in this laboratory (1-13) and in many laboratories throughout the world. We (J.M. and B.N.A.) are currently preparing a compilation of these results, and so far about 85% of the known carcinogens tested have been detected as mutagens in the test, and very few (<10%) noncarcinogens (many close relatives of carcinogens have been tested) are positive. This and other evidence showing that a high percentage of carcinogens are mutagens is most easily explained if carcinogens cause cancer by somatic mutation (4). We believe there is a high probability that chemicals found to be mutagens in the Salmonella test will turn out to be carcinogens.We have recently introduced two new tester strains (TA100 and TA98) which were constructed by transferring to our standard tester strains TA1535 and TA1538 respectively, a res...

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Section: Resultssupporting

confidence: 58%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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

McCann¹,

Simmon²,

Streitwieser³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

147

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“…Induction of (dA-dT)-(dC-dG) and (dCdG)-(dA-dT) transversions from etheno-dA and etheno-dC are consistent with the fact that chloroethylene oxide, chloroacetaldehyde and metabolically activated vinyl chloride induce base-pair-substitution mutations (Rannug et al, 1974;Malaveille et al, 1975;McCann et al, 1975;Phillips et al, 1980), but not frame-shift mutations, in Salmonella typhimurium strains. It follows that the mechanism of vinyl chloride carcinogenicity/ mutagenicity has been studied more intensively than that of any other human carcinogen.…”

Section: Mechanisms Of Vinyl Chloride Carcinogenicity/mutagenicitymentioning

confidence: 65%

Mechanisms of vinyl chloride carcinogenicity/mutagenicity

Hathaway¹

1981

Br J Cancer

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“…4) Mutagenicity studies demonstrated that CAA induced gene mutations in prokaryotic and eukaryotic cells. [5][6][7][8][9] Also, etheno derivatives of nucleic acids were identified as reaction products of CAA with DNA. 10,11) Increased frequencies of sister chromatid exchange (SCE) have been observed in workers who are occupationally exposed to vinyl chloride monomer (VCM).…”

Section: Introductionmentioning

confidence: 99%

Chloroacetaldehyde Induces Chromosome Aberrations and Micronucleus Formation but Not 2-chloroethanol

Liao

Hsu

Matsuura

et al. 2011

JOURNAL OF HEALTH SCIENCE

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2-Chloroethanol (2-CE) has been used on grapevines to accelerate grape growth, and its metabolite, chloroacetaldehyde (CAA), accumulated in the liver and blood from rats intoxicated with 2-CE. Chronic occupational injury might be a possible reason for the 2-CE intoxication. In this study, we used the in vitro and in vivo tests to examine the genotoxicity of 2-CE and CAA. First, 2-CE did not induce chromosome aberration formation in Chinese ovary hamster cells, but CAA did induce chromosome aberration formation, especially the chromosome gap-type aberration after S9 activation. Second, 2-CE at high doses (1/2 LD 50 ), but not at low doses, induced peripheral blood micronucleus formation in mice. CAA induced micronucleus formation at low and high dosages (1/8-1/2 LD 50 ). These results indicated that CAA plays an important role in 2-CE chronic intoxication, and the genotoxic mechanisms of CAA require further study.

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Mutagenicity of vinyl chloride, chloroethyleneoxide, chloroacetaldehyde and chloroethanol

Cited by 173 publications

References 4 publications

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

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

Mechanisms of vinyl chloride carcinogenicity/mutagenicity

Chloroacetaldehyde Induces Chromosome Aberrations and Micronucleus Formation but Not 2-chloroethanol

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