Genotoxic effects of ethylene oxide, propylene oxide and epichlorohydrin in humans: update review (1990–2001)

Kolman, Ada; Chovanec, Miroslav; Osterman-Golkar, Siv

doi:10.1016/s1383-5742(02)00067-4

Cited by 94 publications

(56 citation statements)

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“…The alkyl residues under investigation here are O 6 -hydroxyethyl (heG) and the O 6 -hydroxypropyl isomers (1hpG and 2hpG) that are formed by the reaction with DNA of ethylene and propylene oxides, respectively (Fig. 1A) (23,24). These larger adducts are compared with the more extensively studied O 6 -methylguanine (mG) adduct (1-4).…”

Section: Resultsmentioning

confidence: 99%

“…In the present paper, we have investigated the modulation by MMR and eATL of the genotoxicity of defined O 6 -alkylguanine adducts in E. coli produced by ethylene oxide and propylene oxide, which together with their precursors ethylene and propylene are important raw materials and chemical intermediates (23,24). Adducts under investigation here are O 6 -hydroxyethylguanine (heG), O 6 -1-hydroxypropylguanine (1hpG), and its isomer O 6 -2-hydroxypropylguanine (2hpG).…”

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confidence: 99%

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Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O ⁶ -alkylguanine adducts in Escherichia coli

Mazón

Philippin

Cadet

et al. 2010

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

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O 6 -alkylG adducts are highly mutagenic due to their capacity to efficiently form O 6 -alkylG:T mispairs during replication, thus triggering G→A transitions. Mutagenesis is largely prevented by repair strategies such as reversal by alkyltransferases or excision by nucleotide excision repair (NER). Moreover, methyl-directed mismatch repair (MMR) is known to trigger sensitivity to methylating agents via a mechanism that involves recognition by MutS of the O 6 -mG:T replication intermediates. We wanted to investigate the mechanism by which MMR controls the genotoxicity of environmentally relevant O 6 -alkylG adducts formed by ethylene oxide and propylene oxide. Recently, the alkyltransferase-like gene ybaZ (eATL) was shown to enhance repair of these slightly larger O 6 -alkylG adducts by NER. We analyzed the toxicity and mutagenesis induced by these O 6 -alkylG adducts using single-adducted plasmid probes. We show that the eATL gene product prevents MMR-mediated attack of the O 6 -alkylG:T replication intermediate for the larger alkyl groups but not for methyl. In vivo data are compatible with the occurrence of repeated cycles of MMR attack of the O 6 -alkylG:T intermediate. In addition, in vitro, the eATL protein efficiently prevents binding of MutS to the O 6 -alkylG:T mispairs formed by the larger alkyl groups but not by methyl. In conclusion, eATL not only enhances the efficiency of repair of these larger adducts by NER, it also shields these adducts from MMR-mediated toxicity.futile mismatch repair cycling | interference between repair pathways | nucleotide excision repair | ybaZ gene

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O ⁶ -alkylguanine adducts in Escherichia coli

Mazón

Philippin

Cadet

et al. 2010

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

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“…In test animals, ECH has been shown to cause papillomas and carcinomas (20) and to inhibit spermatogenesis (21). Understanding its mechanism of toxicity may clarify the risk of exposure for the estimated 250,000 industrial workers exposed to this compound annually in the United States alone (16). …”

Section: Introductionmentioning

confidence: 99%

DNA Interstrand Cross-Linking by Epichlorohydrin

Romano

Newman

Zahran

et al. 2007

Chem. Res. Toxicol.

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Epichlorohydrin (ECH), an important industrial chemical, is a bifunctional alkylating agent with the potential to form DNA cross-links. Occupational exposure to this suspect carcinogen leads to chromosomal aberrations, and ECH has been shown previously to undergo reaction with DNA in vivo and in vitro.We used denaturing polyacrylamide gel electrophoresis to monitor the possible formation of interstrand cross-links within DNA oligomers by ECH and the related compound, epibromohydrin (EBH). Although both compounds did indeed form cross-links between deoxyguanosine residues, EBH was a more efficient cross-linker than ECH. The optimal pH for cross-linking also varied, with ECH more efficient at pH 5.0 and EBH more efficient at pH 7.0. Both agents were relatively flexible in the sequences targeted, with comparable efficiencies for 5′-GGC and 5′GC sites. Furthermore, interstrand cross-linking by the two optical isomers of ECH correlated with their relative cytotoxicities, with R-ECH about twice as potent as S-ECH.

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“…The use of this gas necessitates strict precautions as it is considered to be a human carcinogen capable of increasing the incidence of leukemia and/or lymphoma (1)(2)(3)(4)(5). Besides its carcinogenic properties, ethylene oxide is an irritant (6) and may induce abortion (7).…”

Section: Introductionmentioning

confidence: 99%

Exposure to Ethylene Oxide in Hospitals: Biological Monitoring and Influence of Glutathione S-Transferase and Epoxide Hydrolase Polymorphisms

Haufroid

Merz²,

Hofmann³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Ethylene oxide is considered as a human carcinogen. A biomarker of exposure would be a useful instrument to assess the risk in occupationally exposed workers. This cross-sectional study aimed at examining (a) whether the urinary excretion of a metabolite of ethylene oxide, 2-hydroxyethyl mercapturic acid (HEMA), could be used for monitoring occupational exposure and (b) whether glutathione S-transferase (GST) and epoxide hydrolase genotypes influenced biological monitoring. Exposure to ethylene oxide was measured by personal sampling in 80 hospital workers (95% of those eligible). HEMA concentrations were determined in three urine samples (baseline, end of shift, and next morning) by liquid chromatography with tandem mass spectrometry. GSTs (GSTT1, GSTM1, and GSTP1) and epoxide hydrolase (EPHX1) were also genotyped. The influence of exposure, genotypes, and several other factors was examined in multiple regression analyses. Exposure was always <1 parts per million. On a group basis, exposure and a non-null GSTT1 genotype increased the HEMA concentrations in the urine sample collected at the end of the shift and these factors remained statistically significant after considering possible confounding or modifying factors. (Cancer Epidemiol Biomarkers Prev 2007;16(4):796 -802)

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Genotoxic effects of ethylene oxide, propylene oxide and epichlorohydrin in humans: update review (1990–2001)

Cited by 94 publications

References 100 publications

Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O ⁶ -alkylguanine adducts in Escherichia coli

Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O ⁶ -alkylguanine adducts in Escherichia coli

DNA Interstrand Cross-Linking by Epichlorohydrin

Exposure to Ethylene Oxide in Hospitals: Biological Monitoring and Influence of Glutathione S-Transferase and Epoxide Hydrolase Polymorphisms

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Genotoxic effects of ethylene oxide, propylene oxide and epichlorohydrin in humans: update review (1990–2001)

Cited by 94 publications

References 100 publications

Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O 6 -alkylguanine adducts in Escherichia coli

Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O 6 -alkylguanine adducts in Escherichia coli

DNA Interstrand Cross-Linking by Epichlorohydrin

Exposure to Ethylene Oxide in Hospitals: Biological Monitoring and Influence of Glutathione S-Transferase and Epoxide Hydrolase Polymorphisms

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Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O ⁶ -alkylguanine adducts in Escherichia coli

Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O ⁶ -alkylguanine adducts in Escherichia coli