Demethylation of Methyl Mercury in Different Brain Sites of Macaca-fascicularis Monkeys during Long-Term Subclinical Methyl Mercury Exposure

Vahter, Marie; Mottet, N. Karle; Friberg, L; Lind, Sara Bergström; Charleston, Jay S.; Burbacher, Thomas M.

doi:10.1006/taap.1995.1193

Cited by 120 publications

(90 citation statements)

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“…This demethylation was reported to be possible in biological systems using tissue culture or slices (Shapiro and Chan, 2008;Yasutake and Hirayama, 2001). Accumulation of inorganic Hg in the brain has been observed in primates after long-term exposure to MeHgCl (Vahter et al, 1995). In a 22-year follow-up study of a MeHgCl-exposed family in the United States, the detected mercury was almost completely found in the inorganic form (Davis et al, 1994).…”

Section: Toxicological Activity Of Organic and Inorganic Hgmentioning

confidence: 99%

Effects of organic and inorganic mercury(II) on gene expression via DNA conformational changes

Ueda

Makino

Tobe

et al. 2014

Fundam. Toxicol. Sci.

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-The effects of organic and inorganic mercury ions on gene expression were studied by in vitro cell-free assays for transcription and translation. While organic mercury (methylmercury chloride, MeHgCl) showed no effects, treatment of template DNA with inorganic mercury (HgCl 2 ) inhibited mRNA synthesis in a bacteriophage T7 RNA polymerase transcription system. The inhibited transcription resulted in reduced protein synthesis after the subsequent application of the transcripts to a translation system consisting of Sf21 insect cell lysate. Treatment of mRNA with inorganic mercury also reduced translation, although this inhibitory effect was weaker than the effect produced by DNA exposure. Treatment of DNA and RNA with mercury did not increase oxidative damage such as strand cleavage and base oxidation. Instead, circular dichroism spectrometry demonstrated that mercury ions, not methyl mercury, drastically changed strand conformation of DNA and RNA. Therefore, the gene expression inhibition observed in this study was thought to be caused by crossbridging of DNA bases with mercury ions, which blocked the transcriptional machinery. Taken together with reports on biological conversion of organic mercury to inorganic forms in animals, our results show that transcriptional inhibition via conformational changes in DNA could be a toxic mechanism involved in mercury poisoning.

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Section: Toxicological Activity Of Organic and Inorganic Hgmentioning

confidence: 99%

Effects of organic and inorganic mercury(II) on gene expression via DNA conformational changes

Ueda

Makino

Tobe

et al. 2014

Fundam. Toxicol. Sci.

View full text Add to dashboard Cite

show abstract

“…Accumulation in the adult studies ranged from 0 to 0.077% of the ingested quantity relative to brain and body mass. Interestingly, the internal doses reported by Charleston et al (1996) were about 2-3 fold higher than those reported by Vahter et al (1994).…”

Section: Accumulation In the Cns From Oral Exposurementioning

confidence: 64%

“…There is overwhelming support for the theory of demethylation of MeHg in mammalian systems (Allen et al, 2001;Charleston et al, 1996;Hansen & Danscher, 1995;Monnet-Tschudi et al, 1996;Vahter et al, 1994;Vahter et al, 1995;Watanabe, 2002;Yasutake & Hirayama, 2001). The different rates of elimination of the two mercury species (Dringen et al, 1999;Yasutake et al, 1998) suggest that demethylation is a detrimental consequence.…”

Section: General Thesis Objectivementioning

confidence: 99%

“…Reported averages were used when brain and body masses were not given. 1994) (Vahter et al, 1994) (Vahter et al, 1994) (Vahter et al, 1994) (Vahter et al, 1994) (Vahter et al, 1994) (Vahter et al, 1994) (Vahter et al, 1994) (Charleston et al, 1996) (Charleston et al, 1996) (Charleston et al, 1996) (Charleston et al, 1996) Using the chemical abstracts database for MeHg from SciFinder Scholar and the keywords accumulation and brain, we found 21 examples of MeHg dosing ranging from 0.84mg/kg/day to 5mg/kg/day, in rats, for a period ranging from 1 to 30 days. External doses ranged from.l to 150 mg/kg and internal doses ranged from 0.22 to 30.4 u.g/g.…”

Section: Accumulation In the Cns From Oral Exposurementioning

confidence: 99%

“…However, demethylation has been seen observed over time in both animal models (Charleston et al, 1996;Pamphlett & Coote, 1998;Vahter et al, 1995) and human populations (Eto, 2000;Amin-Zaki et al, 1974). The determining factors for the process of demethylation, particularly in the CNS, are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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