Mutagenicity and cytotoxicity of 2-methoxyethanol and its metabolites in Chinese hamster cells (the CHO/HPRT and AS52/GPT assays)

Ma, Hongbao; An, Jie; Hsie, Abraham W.; Au, William W.

doi:10.1016/0165-1218(93)90044-e

Cited by 30 publications

(10 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2-ME or its derivatives had apparently mutagenic properties as well, which had been doubted before [34]. Confirmation was obtained in further experiments and more recently by cell-line experiments [35,36]. Because of the large resemblance of the terata of the mother-fly and the mutant phenotype of the daughters, my very first thought was that the novel Notch mutation was a first and clear example of inheritance of an acquired character [37].…”

Section: Introductionmentioning

confidence: 89%

See 1 more Smart Citation

Concurrent teratogenic and mutagenic action of 2‐methoxyethanol in Drosophila melanogaster larvae resulted in similar phenotypes: Close resemblance to directed mutations

Eisses

1999

Teratog. Carcinog. Mutagen.

View full text Add to dashboard Cite

Early third instar larvae of wild-type Drosophila melanogaster were transferred to medium supplemented with 2-methoxyethanol (2-ME) or ethylene glycol monomethyl ether. 2-ME produced terata in adult flies as wing notches and duplications of macrochaetae similar to feeding with methoxyacetic acid (MAA), the oxidation product of 2-ME. Larval feeding with 2-ME also affected the fertility of both females and males. 2-ME or more likely its intermediate oxidation product, methoxyacetaldehyde (MAALD), concurrently generated mutations in the premeiotic stages of the oocytes in the early third instar larvae. The mutagenicity of 2-ME has been confirmed in subsequent small scale experiments. The mutation frequency ranged from 4 x 10(-4) to 1 x 10(-2). Although terata were not supposed to be heritable, 1.1 to 8.7% of the affected females produced offspring with phenotypic similarity to the female parent. This phenomenon looked like a classical example of inheritance of an acquired character. The question is addressed why a Notch-like phenocopy, generated by larval 2-ME treatment, could bring forth Notch and rudimentary mutants in particular. Administration of 2-ME to larvae, containing the highly active alcohol dehydrogenase variant ADH-71k, exposed the mitotic germ cells and the mitotic somatic cells of the imaginal discs simultaneously to the mutagen MAALD and the teratogen MAA, respectively. The chances for specific gene mutations, though non-adaptive, were likely increased by a feedback mechanism: gene-products that were inhibited or disturbed by the teratogen demanded increased transcription of their encoding genes. Transcribed genes are more susceptible to mutagens.

show abstract

Section: Introductionmentioning

confidence: 89%

“…The mutagenicity of 2-ME was doubted as such after a standard SLRL-test with D. melanogaster male flies [34]. Recently, methoxyacetaldehyde (MAALD) proved mutagenic in cell-line experiments [35,36]. MAALD was likely to be present in D. melanogaster larvae as the intermediate product of 2-ME oxidation into MAA by ADH-71k activity [25,31].…”

Section: Mutagenesismentioning

confidence: 99%

Concurrent teratogenic and mutagenic action of 2‐methoxyethanol in Drosophila melanogaster larvae resulted in similar phenotypes: Close resemblance to directed mutations

Eisses

1999

Teratog. Carcinog. Mutagen.

View full text Add to dashboard Cite

show abstract

“…131 mmol/l, entspricht 10 mg/ml), aber keine Genmutationen am HPRT-Locus berichtet (Elias et al 1996). Auch am HPRT-Locus von CHO-Zellen sowie am GPT-Locus von CHO-AS52-Zellen induzierte 2-Methoxyethanol keine Genmutationen (Ma et al 1993). 2-Methoxyethanol verursachte bis 100 mg/ml keine Genmutationen im TK +/--Mutationstest mit L5178Y-Mauslymphomzellen in Anwesenheit eines metabolischen Aktivierungssystems (BUA 1997).…”

Section: -Methoxyethanolunclassified

“…Methoxyessigsäure induzierte keine Genmutationen am HPRT-Locus von CHO-K1-BH4-Zellen bis 200 mmol/l (18 mg/ml) ohne metabolische Aktivierung oder bis 100 mmol/l (9 mg/ml) mit metabolischer Aktivierung. Auch am GPT-Locus von CHO-AS52-Zellen führte Methoxyessigsäure bei bis zu 100 mmol/l (9 mg/ml) ohne metabolische Aktivierung zu keinen Genmutationen (Ma et al 1993). …”

Section: Methoxyessigsäureunclassified

2‐Methoxyethanol [MAK Value Documentation in German language, 2009]

2012

The MAK‐Collection for Occupational Health and Safety

View full text Add to dashboard Cite

Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 47. Lieferung, Ausgabe 2009 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Toxikokinetik und Metabolismus Aufnahme, Verteilung, Ausscheidung PBPK‐Modell/Monte‐Carlo‐Simulation: Metabolismus Biomonitoring Erfahrungen beim Menschen Hämatologische Effekte Hepatotoxische Effekte Reproduktionstoxische Effekte Genotoxizität Kanzerogenität Tierexperimentelle Befunde und In‐vitro‐Untersuchungen Subakute, subchronische und chronische Toxizität Wirkung auf Haut und Schleimhäute Allergene Wirkung Reprodu ktionstoxizität Fertilität Entwicklungstoxizität Genotoxizität In vitro In vivo Kanzerogenität Bewertung

show abstract

“…It is used in products such as epoxy resin coatings, inks, cleaning agents as well as aviation fluids (NIOSH, 1991). ME has been shown to cause a diverse range of toxic effects in experimental animals and humans, including hematotoxicity (Cohen, 1984;Grant et al, 1985), reproductive toxicity(We1ch et al, 1988), developmental toxicity(H0rton et al, 1985) and genotoxicity (Ma et al, 1993). ME-induced immunotoxicity is considered to be caused by its metabolites, 2-methoxyacetaldehyde(MAAD) and 2-methoxyacetic acid(MAA) (Kim and Smialowicz, 1997).…”

mentioning

confidence: 99%

2-methoxyetunol-induced apoptosis in rat thymus

Ju²,

Pyo³

et al.

Proceedings Third Russian-Korean International Symposium on Science and Technology. KORUS'99 (Cat. No.99EX362)

View full text Add to dashboard Cite

2-MethoxyethanoI(ME) is an industrial solvent, which has been shown to cause immunosuppression and atrophy of thymus in the experimental animals. However, the mechanism of which ME produces immunosuppression has not been reported. In this study, we report that ME produces immunosuppression by inducing apoptosis of thymus. The thymus weight and cellularity was decreased by oral treatment of ME. By histopathological examination, we found that the thymus of ME-treated rats have apoptotic cells while those of control rats have not. ME and its metabolites 2-methoxyacetaldehyde(MAAD) and 2-methoxyacetic acid(MAA) produced dose-dependent decrease of cell viabilities in cultured thymocytes. By microscopic observation, we determined that ME, MAAD and MAA treated thymocytes produced shrinkage of nucleus, membrane blebbings, which are characteristics of apoptotic cell death. These results suggest that ME produces immunosuppression by inducing apoptosis in thymocytes.

show abstract

Mutagenicity and cytotoxicity of 2-methoxyethanol and its metabolites in Chinese hamster cells (the CHO/HPRT and AS52/GPT assays)

Cited by 30 publications

References 22 publications

Concurrent teratogenic and mutagenic action of 2‐methoxyethanol in Drosophila melanogaster larvae resulted in similar phenotypes: Close resemblance to directed mutations

Concurrent teratogenic and mutagenic action of 2‐methoxyethanol in Drosophila melanogaster larvae resulted in similar phenotypes: Close resemblance to directed mutations

2‐Methoxyethanol [MAK Value Documentation in German language, 2009]

2-methoxyetunol-induced apoptosis in rat thymus

Contact Info

Product

Resources

About