Methyl bromide causes DNA methylation in rats and mice but fails to induce somatic mutations in λlacZ transgenic mice

Pletsa, Vasiliki; Steenwinkel, M.J.S.T.; Delft, J.H.M. van; Baan, R.A.; Kyrtopoulos, Soterios A.

doi:10.1016/s0304-3835(98)00262-6

Cited by 17 publications

(6 citation statements)

References 25 publications

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“…36 Indeed, methyl bromide can directly methylate calf thymus DNA in aqueous solution. 37 Moreover, methyl bromide causes aberrant DNA methylation in rats and mice in vivo, 109,110 and can generate the highly mutagenic O 6 -methyl guanine lesion. 37,109 Glutathione conjugation of methyl bromide is the primary mechanism of its detoxification and this reaction is catalyzed by the glutathione S-transferase theta-1 (GSTT1) isoform.…”

Section: Prostate Cancermentioning

confidence: 99%

“…37 Moreover, methyl bromide causes aberrant DNA methylation in rats and mice in vivo, 109,110 and can generate the highly mutagenic O 6 -methyl guanine lesion. 37,109 Glutathione conjugation of methyl bromide is the primary mechanism of its detoxification and this reaction is catalyzed by the glutathione S-transferase theta-1 (GSTT1) isoform. 111 The frequency of the GSTT1 null polymorphism in the human population is 20% for whites and 80% for Asians; these individuals do not express a functional GSTT1 enzyme.…”

Section: Prostate Cancermentioning

confidence: 99%

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Increased cancer burden among pesticide applicators and others due to pesticide exposure

Alavanja

Ross

Bonner

2013

CA A Cancer J Clinicians

297

213

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A growing number of well-designed epidemiological and molecular studies provide substantial evidence that the pesticides used in agricultural, commercial, and home and garden applications are associated with excess cancer risk. This risk is associated both with those applying the pesticide and, under some conditions, those who are simply bystanders to the application. In this article, the epidemiological, molecular biology, and toxicological evidence emerging from recent literature assessing the link between specific pesticides and several cancers including prostate cancer, non-Hodgkin lymphoma, leukemia, multiple myeloma, and breast cancer are integrated. Although the review is not exhaustive in its scope or depth, the literature does strongly suggest that the public health problem is real. If we are to avoid the introduction of harmful chemicals into the environment in the future, the integrated efforts of molecular biology, pesticide toxicology, and epidemiology are needed to help identify the human carcinogens and thereby improve our understanding of human carcinogenicity and reduce cancer risk. CA Cancer J Clin 2013;63:120-142.

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Section: Prostate Cancermentioning

confidence: 99%

Section: Prostate Cancermentioning

confidence: 99%

Increased cancer burden among pesticide applicators and others due to pesticide exposure

Alavanja

Ross

Bonner

2013

CA A Cancer J Clinicians

297

213

View full text Add to dashboard Cite

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“…The strong alkylating potency of methyl bromide is primarily responsible for its cytotoxic effect, causing this pesticide to be classified as a potent stimulator of cell growth and, therefore, a potential tumor promoter. Distinguishing alkylation from metabolic incorporation provides proof for the direct genotoxic effect of methyl bromide, methyl iodide and other methyl halides [46-48]. Based on in-vivo and in-vitro studies, methyl bromide induces gene mutations in bacteria, mice and humans.…”

Section: Resultsmentioning

confidence: 99%

“…Effects such as DNA single strand breaks after methyl halide intoxication can, however, point to both genotoxic as well as non-genotoxic mechanisms [24]. Methyl bromide causes DNA methylation in rats and mice with concominant decreases in the activity of O 6 -alkylguanine-DNA-alkyltransferase [48]. Interestingly more recent data show that O 6 -alkylguanine-DNA-alkyltransferase has opposing effects in modulating the genotoxicity of dibromomethane, suggesting a pathway which is alternative to the well-recognized pathway that involves activation by GSTs [49].…”

Section: Resultsmentioning

confidence: 99%

Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

Budnik¹,

Kloth²,

Velasco-Garrido

et al. 2012

Environ Health

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BackgroundAlthough ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage). The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity.MethodsWe performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic) or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis.ResultsOut of the 542 peer reviewed publications between 1990-2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49), P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage.ConclusionsBoth the epidemiological evidence and toxicological data suggest a possible link between methyl bromide exposure and serious health problems, including prostate cancer risk from occupational and community exposure. The environmental risks of methyl bromide are not in doubt, but also its health risks, especially for genetically predisposed subjects, should not be underestimated.

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“…Negative results were obtained also in the examined organs including liver and bone marrow in the Muta™mouse assay. However, DNA methylation in the liver was observed in the same assay even at lower dose levels [60] indicating differences in the sensitivity of these two genotoxic endpoints. The mouse micronucleus test revealed chromosome mutagenic activity [61] although results of other in vivo tests are equivocal (see Additional file 1).…”

Section: Resultsmentioning

confidence: 99%

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et al. 2005

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As part of a larger literature study on transgenic animals in mutagenicity testing, test results from the transgenic mutagenicity assays (lacI model; commercially available as the Big Blue® mouse, and the lacZ model; commercially available as the Muta™Mouse), were compared with the results on the same substances in the more traditional mouse bone marrow micronucleus test. 39 substances were found which had been tested in the micronucleus assay and in the above transgenic mouse systems. Although, the transgenic animal mutation assay is not directly comparable with the micronucleus test, because different genetic endpoints are examined: chromosome aberration versus gene mutation, the results for the majority of substances were in agreement. Both test systems, the transgenic mouse assay and the mouse bone marrow micronucleus test, have advantages and they complement each other. However, the transgenic animal assay has some distinct advantages over the micronucleus test: it is not restricted to one target organ and detects systemic as well as local mutagenic effects.

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Methyl bromide causes DNA methylation in rats and mice but fails to induce somatic mutations in λlacZ transgenic mice

Cited by 17 publications

References 25 publications

Increased cancer burden among pesticide applicators and others due to pesticide exposure

Increased cancer burden among pesticide applicators and others due to pesticide exposure

Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

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