The role of glutathione in the bacterial mutagenicity of vapour phase dichloromethane

Dillon, Debbie; Edwards, Ian; Combes, Robert; McConville, Malcolm J.; Zeiger, Errol

doi:10.1002/em.2850200310

Cited by 12 publications

(4 citation statements)

References 37 publications

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“…However, they report that there is no evidence of carcinogenicity to rats or mice, though the experiments were flawed by duration and dosage considerations (IARC 1987d). 5 Dillon et al, 1992. 6 Garner, 1980.…”

Section: Carcinogens Detected By the T1 Assay Not Detected By The Bacmentioning

confidence: 99%

In vitro determination of carcinogenicity of sixty‐four compounds using a bovine papillomavirus DNA‐carrying C3H/10T½ cell line

Kowalski¹,

Laitinen²,

Mortazavi‐Asl³

et al. 2000

Environ. Mol. Mutagen.

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A new in vitro test for predicting rodent carcinogenicity is evaluated against a testing database of 64 chemicals including both genotoxic and nongenotoxic carcinogens and carcinogens that normally require addition of an S-9 microsomal fraction for detection in the bacterial mutagenicity assay. The assay uses focus formation in a stable, bovine papillomavirus type 1 (BPV-1) DNA carrying C3H/10T(1/2) mouse embryo fibroblast cell line (T1) that does not require transfection, infection with virus, isolation of primary cells from animals, or addition of a microsomal fraction. Of a total database of 64 compounds, 92% of the carcinogens, promoters, or noncarcinogens were correctly predicted. Based on previously reported results, the test of bacterial mutagenicity would have correctly predicted 58% of carcinogens, promoters or noncarcinogens and the Syrian hamster embryo test would have correctly predicted 87% of carcinogens, promoters, or noncarcinogens of this database. Of carcinogens that normally require addition of an S-9 fraction, T1 cells correctly predicted rodent carcinogenicity of polyaromatic hydrocarbons, aflatoxins, azo-compounds, nitrosamines, and hydrazine without the addition of an S-9 fraction. Of nongenotoxic carcinogens, T1 cells correctly predicted diethylstilbestroel, diethylhexylphthalate, acetamides, alkyl halides, ethyl carbamate, and phorbol ester tumour promoters.

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Section: Carcinogens Detected By the T1 Assay Not Detected By The Bacmentioning

confidence: 99%

In vitro determination of carcinogenicity of sixty‐four compounds using a bovine papillomavirus DNA‐carrying C3H/10T½ cell line

Kowalski¹,

Laitinen²,

Mortazavi‐Asl³

et al. 2000

Environ. Mol. Mutagen.

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“…aliphatics, aromatics and other (11) tetradecanoyl-phorbol-13-acetate* S P 0. Dillon et al, 1992. 6 Garner, 1980.…”

Section: Carcinogens Detected By the T1 Assay Not Detected By The Bacmentioning

confidence: 99%

In vitro determination of carcinogenicity of sixty-four compounds using a bovine papillomavirus DNA-carrying C3H/10T� cell line

Kowalski¹,

Laitinen²,

Mortazavi-Asl³

et al. 2000

Environ. Mol. Mutagen.

View full text Add to dashboard Cite

A new in vitro test for predicting rodent carcinogenicity is evaluated against a testing database of 64 chemicals including both genotoxic and nongenotoxic carcinogens and carcinogens that normally require addition of an S‐9 microsomal fraction for detection in the bacterial mutagenicity assay. The assay uses focus formation in a stable, bovine papillomavirus type 1 (BPV‐1) DNA carrying C3H/10T½ mouse embryo fibroblast cell line (T1) that does not require transfection, infection with virus, isolation of primary cells from animals, or addition of a microsomal fraction. Of a total database of 64 compounds, 92% of the carcinogens, promoters, or noncarcinogens were correctly predicted. Based on previously reported results, the test of bacterial mutagenicity would have correctly predicted 58% of carcinogens, promoters or noncarcinogens and the Syrian hamster embryo test would have correctly predicted 87% of carcinogens, promoters, or noncarcinogens of this database. Of carcinogens that normally require addition of an S‐9 fraction, T1 cells correctly predicted rodent carcinogenicity of polyaromatic hydrocarbons, aflatoxins, azo‐compounds, nitrosamines, and hydrazine without the addition of an S‐9 fraction. Of nongenotoxic carcinogens, T1 cells correctly predicted diethylstilbestroel, diethylhexylphthalate, acetamides, alkyl halides, ethyl carbamate, and phorbol ester tumour promoters. Environ. Mol. Mutagen. 35:300–311, 2000 © 2000 Wiley‐Liss, Inc.

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“…Dichloromethane is mutagenic in some, but not all, shortterm mutagenicity assays (for review, see ref 1). Dichloromethane is also mutagenic in Salmonella typhimurium (2), and the bacterial mutagenicity of dichloromethane is associated with its glutathione-dependent bioactivation (3)(4)(5). Indeed, the mutagenicity of dichloromethane is markedly enhanced in S. typhimurium TA1535 transfected with a plasmid vector containing the cDNA for rat glutathione S-transferase 5-5 (6).…”

Section: Introductionmentioning

confidence: 99%

Bioactivation of [13C]Dichloromethane in Mouse, Rat, and Human Liver Cytosol: 13C Nuclear Magnetic Resonance Spectroscopic Studies

Hashmi¹,

Dechert²,

Dekant³

et al. 1994

Chem. Res. Toxicol.

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Dichloromethane is tumorigenic in lungs and liver of B6C3F1 mice, but is not tumorigenic in rats or hamsters, and its toxicity is associated with glutathione-dependent bioactivation. The objective of the present studies was to investigate the glutathione-dependent bioactivation of [13C]dichloromethane in mouse, rat, and human liver cytosol and the fate of dichloromethane-derived reactive intermediates with 13C NMR. [13C]Formaldehyde hydrate, [13C]S-(hydroxymethyl)glutathione, and [13C]methanol were identified as metabolites of [13C]dichloromethane. [13C]S-(Chloromethyl)glutathione, a putative intermediate in the glutathione-dependent bioactivation of dichloromethane, or derived adducts were not observed. Moreover, no evidence for the formation of S,S'-methylenebis[glutathione] by reaction of glutathione and formaldehyde under physiological conditions was obtained, although methanol was observed as a product. S,S'-Methylenebis[glutathione] was, however, formed by reaction of glutathione and formaldehyde at pH 1. S-(Chloromethyl)-N-acetyl-L-cysteine methyl ester, a surrogate for S-(chloromethyl)glutathione, was prone to hydrolysis. These results corroborate the finding that formaldehyde is a reactive intermediate formed during the glutathione-dependent bioactivation of dichloromethane that may be involved in the observed tumorigenicity of dichloromethane in susceptible species. The results also indicate that S-(chloromethyl)glutathione is an intermediate in the glutathione-dependent bioactivation of dichloromethane and may also play a role in its mutagenicity and carcinogenicity.

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The role of glutathione in the bacterial mutagenicity of vapour phase dichloromethane

Cited by 12 publications

References 37 publications

In vitro determination of carcinogenicity of sixty‐four compounds using a bovine papillomavirus DNA‐carrying C3H/10T½ cell line

In vitro determination of carcinogenicity of sixty‐four compounds using a bovine papillomavirus DNA‐carrying C3H/10T½ cell line

In vitro determination of carcinogenicity of sixty-four compounds using a bovine papillomavirus DNA-carrying C3H/10T� cell line

Bioactivation of [13C]Dichloromethane in Mouse, Rat, and Human Liver Cytosol: 13C Nuclear Magnetic Resonance Spectroscopic Studies

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