The cytotoxicity of methylmercuric hydroxide and colchicine in cultured mouse neuroblastoma cells

Koerker, Robert L.

doi:10.1016/0041-008x(80)90358-0

Cited by 27 publications

(7 citation statements)

References 25 publications

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“…At 7.5 x lo-' M , nuclear and cell toxicity was complete after 11 days of exposure. This is in contrast with the values of 2.5 x M (0.05 ppm) MMC (Ramel 1974) in plants and 2 X M (Koerker 1980) in neuroblastoma mouse cells stated as the lowest concentrations which produce significant mitotic changes. Chlorella agar cultures exposed to MMC for 15 days had 53.8% survival at 1.0 x 104ppm and 0% survival at 1.0 X ppm (Rai and Dey 1980 the process of MMC toxicity under long-term exposure at each concentration proceeds via a different combination of inhibitory and (or) toxic processes.…”

Section: Discussioncontrasting

confidence: 73%

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Interactive patterns of methyl mercury toxicity in nuclear and cell division of apical meristems of Elodea densa at low concentrations and long-term exposures in vivo

Czuba¹,

Mortimer²

1982

Can. J. Bot.

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CZUBA, M., and D. C. MORTIMER. 1982. Interactive patterns of methyl mercury toxicity in nuclear and cell division of apical meristems of Elodea densa at low concentrations and long-term exposures in vivo. Can. J. Bot. 60: 657-666. Elodea densa plants continuously exposed to low levels of methylmercury (7.5 X lo-'' to 7.5 X lo-' M) in a flowing water system over a 25-day period concentrated methylmercury in young tissues. Toxicity effects in apical meristems were not linear with dose and time but were interactive in response. Microscopic studies of plants treated at 7.5 X 10-'OM showed a predominance of "spaghetti" prophases, a gradual inhibition of mitosis, and imbalance of mitotic stages. Higher concentrations of methylmercury produced different effects: bi-and multi-nucleate cells, polyploidy , aneuploidy , and altered or incomplete cell walls. At the highest concentrations (7.5 X 10-'M) total pycnosis developed in the apex within 11 days, followed by a disintegration of nuclear and cell contents. Demethylation in tissues was directly related to methylmercury concentrations in the tissues and to tissue age.

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Section: Discussioncontrasting

confidence: 73%

“…Therefore, they represent mechanisms which cannot be conveniently adapted to explain those effects which occur in organisms under exposure in their native ecological systems. This concept is supported by recent work done on neuroblastoma mouse cells (Koerker 1980) in which a multiple site toxicity of MMC action is suggested.…”

Section: Discussionmentioning

confidence: 61%

Interactive patterns of methyl mercury toxicity in nuclear and cell division of apical meristems of Elodea densa at low concentrations and long-term exposures in vivo

Czuba¹,

Mortimer²

1982

Can. J. Bot.

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“…Sperm concentration and total sperm counts were significantly reduced for only two treated animals. We expected a decrease in sperm production based on the known inhibitory effects of MeHg on cellular mitosis (Rozynkowa & Raczkiewicz 1977;Miura et al 1978;Prasad et al 1979;Koerker 1980). We could not rule out such an effect in our experiments due to one or more of many uncontrolled variables.…”

Section: Bww-dilutedmentioning

confidence: 93%

Effects of Methyl Mercury on Testicular Functions in Macaca fascicularis Monkeys

1987

Pharmacology & Toxicology

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These studies were performed to investigate the effects of MeHg on testicular function in Macaca fascicularis monkeys. In an in vivo study involving oral treatment of adult males Macaca fascicularis monkeys with MeHg for 20 weeks, changes in spermatozoal production, motility and morphology and in serum testosterone were followed before, during and after treatment. MeHg treatment significantly decreased % motile spermatozoa and scores for sperm speed and forward progression and increased % abnormal sperm tail forms, at sub-neurotoxic levels. The MeHg-induced increase in semen abnormalities was not accompanied by any significant changes in serum levels of testosterone. No consistent histological abnormalities were detected in testicular biopsies from the treated animals at the end of the treatment period. A good recovery pattern was observed for the MeHg effects on sperm motility while this was unclear for the effects on sperm morphology.

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“…In addition, MeHg effects on the mitotic apparatus have been observed repeatedly to cause mitotic aberrations in plant cells (Ramel 1969), human leukocytes (Fiskesjo 1979), and meiosis of mouse ova in vitro (Jagiello & Lin 1973). Inhibition of mitosis has been observed in several cell culture systems after either short term treatment (hours) (Rozynkowa & Raczkiewicz 1977;Miura et al 1979) or longer treatment (days) (Prasad et al 1979;Koerker 1980). Because microtubules are a major component of mitotic spindles, as well as being involved in other cell processes, several investigators (Abe et al 1975;Imura et al 1980;Sager et al 1983) proposed that methyl mercury might interact directly and specifically with microtubules.…”

mentioning

confidence: 99%

Analysis of Methyl Mercury Binding Sites on Tubulin Subunits and Microtubules

Vogel

Margolis

Mottet

1989

Pharmacology & Toxicology

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We have studied the localization and affinity of methyl mercury hydroxide (MeHg) binding sites on microtubules. There is one class of binding sites for MeHg on tubulin, a high affinity class with fifteen sites. MeHg binds to tubulin stoichiometrically within microtubules, and does not induce microtubule disassembly at this low binding ratio. MeHg binds in microtubules either in the presence or absence of free tubulin subunits but free subunits act as uncompetitive inhibitors for MeHg binding to the polymer. These stoichiometric polymer surface binding sites for MeHg apparently do not interfere with subsequent polymerization, in contrast to the multiple sites in the free dimer whose occupation blocks subsequent assembly. In assembly cycles that follow MeHg binding to polymers, we continue to find MeHg bound to microtubules at substoichiometric ratios. Dimers with higher levels of MeHg binding are rendered assembly incompetent. These results show MeHg to have one class of binding site on tubulin, and the MeHg binding site, both to the polymer surface and to the free dimer, to be the same.

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The cytotoxicity of methylmercuric hydroxide and colchicine in cultured mouse neuroblastoma cells

Cited by 27 publications

References 25 publications

Interactive patterns of methyl mercury toxicity in nuclear and cell division of apical meristems of Elodea densa at low concentrations and long-term exposures in vivo

Interactive patterns of methyl mercury toxicity in nuclear and cell division of apical meristems of Elodea densa at low concentrations and long-term exposures in vivo

Effects of Methyl Mercury on Testicular Functions in Macaca fascicularis Monkeys

Analysis of Methyl Mercury Binding Sites on Tubulin Subunits and Microtubules

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