Modifying effects of inactivated bovine serum on the acute toxicity of methylmercuric chloride in cells cultured in vitro.

Dynamics of the killing of Ehrlich's murine ascites tumor cells by methylmercuric chloride, MMC, were investigated. Thresholds in the killing action of MMC were observed in the MMC treatment concentration, but not in the MMC treatment time. Inactivated bovine serum protected the E-cells from killing by MMC in vitro. The apparent MMC toxicity was reduced as the serum concentration increased, but remaining partially at high concentrations. Thus the serum increases the threshold for MMC toxicity. It was confirmed that the mode of action, observed as the kinetics of the acute lethality by suspicious substances, could be examined promptly on the mammalian cell level by the present experimental system.     

Effects of methylmercuric chloride administered to pregnant rats during the preimplantation period

Female rats were treated on Day 1, 2, 3, 4, or 5 of pregnancy with 5 mg/kg methylmercuric chloride ip. Some dams were killed on Day 5 of gestation in order to evaluate toxic effects on the early embryos or blastocysts. The remaining rats were sacrificed at the end of pregnancy to verify any embryofetotoxic and teratogenic effects. Unlike what has been found by other authors with in vitro experiments, no clear toxic effects in the blastocyst on Day 5 of pregnancy were evident. A slight embryofetotoxic effect was found when the females were killed at the end of pregnancy.     

Toxicokinetics of methylmercury and mercuric chloride in mouse embryosin vitro

2: passed away on May 5, 1990.     

氯化三丁基锡对体外培养小鼠胚胎毒性研究

目的观察氯化三丁基锡的体外培养小鼠胚胎毒性。方法采用全胚胎培养技术,将8.5 d龄昆明种小鼠胚胎置入含有不同浓度氯化三丁基锡的大鼠离心血清中旋转培养48 h,观察体外培养小鼠胚胎生长发育和组织器官形态分化的变化。结果氯化三丁基锡在0.05 mg/L以上时能诱发卵黄囊生长和血管分化不良,胚胎发育异常率增高;高浓度组能诱发脑小、心脏畸形(心小和心包积液)、前肢芽小或无、无后肢芽。结论体外实验条件下,氯化三丁基锡对小鼠胚胎具有胚胎毒性和致畸性。     

Vitamin E and vitamin C alter the effect of methylmercuric chloride on neuroblastoma and glioma cells in culture

Vitamin E completely protected glioma cells (C-6) against methylmercuric chloride (CH₃HgCl)-induced toxicity; whereas it produced no such effect on neuroblastoma cells (NBP₂) in culture. Sodium ascorbate (Vitamin C) did not alter the effect of CH₃HgCl on glioma cells, but it markedly enhanced the effect of CH₃HgCl on NB cells. In addition, glioma cells released factor(s) into the medium which increased the cytoxicity of CH₃HgCl on glioma cells and on NB cells (NBA₂₍₁₎).     

Effects of methylmercuric chloride in the presence of cyclic AMP-stimulating agents on glioma and neuroblastoma cells in culture.

The intracellular level of adenosine 3′, 5′-cyclic monophosphate (cyclic AMP) increased in rat glioma (C-6) and mouse neuroblastoma cells (NBP₂) after treatment with methylmercuric chloride (CH₃HgCl). The effects of CH₃HgCl in the presence of cyclic AMP-stimulating agents on glioma cells were in part different from those on NB cells. CH₃HgCl increased prostaglandin E₁ (PGE₁)-induced growth inhibition (due to reduction in cell division and cell death) in glioma and NB cells. CH₃HgCl did not reduce PGE₁-induced formation of cytoplasmic processes in glioma cells except at a higher PGE₁ concentration, but it did decrease PGE₁-induced neurite formation in NB cells. The inhibitors of cyclic nucleotide phosphodiesterase completely prevented the cytotoxic effect of CH₃HgCl on glioma cells, but they markedly enhanced the growth inhibitory effect of CH₃HgCl on NB cells.     

Histochemical demonstration of mercury in the olfactory system of salmon (Salmo salar L.) following treatments with dietary methylmercuric chloride and dissolved mercuric chloride

The deposition of organic and inorganic mercury compounds was studied histochemically in the salmon (Salmo salar L.) olfactory system. One group of salmon was given fodder pellets containing methylmercuric chloride (CH3HgCl, 99 micrograms Hg/g) for 4 weeks. Other groups of fish were exposed to dissolved mercuric chloride (HgCl2, 270 micrograms Hg/liter) for 2, 6, and 12 hr, respectively. In both series of experiments, the radioisotope 203Hg was included in order to determine the accumulation of mercury in the olfactory system. Gamma-spectrometry showed that both mercury compounds accumulated in the olfactory rosettes and their nerves. Tissue sections from the rosettes and olfactory nerves were subjected to autometallographic silver enhancement, thereby rendering mercury deposits visible for light and electron microscopy. Microscopic analysis demonstrated an intense and comprehensive Hg deposition in the axons and Schwann cells of both methylmercury- and inorganic mercury-exposed fish. On the other hand, the two mercury compounds showed different staining patterns in the sensory epithelium. The silver grains evoked by methylmercury were localized predominantly in lysosome-like inclusions within the receptor cells, while those produced by HgCl2 exposure were situated mainly along the borders of neighboring cells. The present findings that organic and inorganic mercury compounds were deposited in the olfactory system along its whole length, from the receptor cell apices to the brain, support the electrophysiological results presented elsewhere (Baatrup et al., 1990, Ecotoxicol. Environ. Safety 20, 269-276).     

Histochemical demonstration of mercury in the olfactory system of salmon (Salmo salar L.) following treatments with dietary methylmercuric chloride and dissolved mercuric chloride

The deposition of organic and inorganic mercury compounds was studied histochemically in the salmon Salmo salar L. olfactory system. One group of salmon was given fodder pellets containing methylmercuric chloride (CH₃HgCl, 99 μg Hg/g) for 4 weeks. Other groups of fish were exposed to dissolved mercuric chloride (HgCl₂, 270 μg Hg/liter) for 2, 6, and 12 hr, respectively. In both series of experiments, the radioisotope ²⁰³Hg was included in order to determine the accumulation of mercury in the olfactory system. Gamma-spectrometry showed that both mercury compounds accumulated in the olfactory rosettes and their nerves. Tissue sections from the rosettes and olfactory nerves were subjected to autometallographic silver enhancement, thereby rendering mercury deposits visible for light and electron microscopy. Microscopic analysis demonstrated an intense and comprehensive Hg deposition in the axons and Schwann cells of both methylmercury- and inorganic mercury-exposed fish. On the other hand, the two mercury compounds showed different staining patterns in the sensory epithelium. The silver grains evoked by methylmercury were localized predominantly in lysosome-like inclusions within the receptor cells, while those produced by HgCl₂ exposure were situated mainly along the borders of neighboring cells. The present findings that organic and inorganic mercury compounds were deposited in the olfactory system along its whole length, from the receptor cell apices to the brain, support the electrophysiological results presented elsewhere (Baatrup et al., 1990, Ecotoxicol. Environ. Safety 20, 269–276).     

Cadmium-induced fetal growth retardation in the mouse

Exposure of mice to 10, 20, or 40 ppm cadmium in their drinking water throughout pregnancy resulted in various degrees of fetal growth retardation. The newborn mice, as well as being smaller than normal, were severely anemic. Parenterally administered iron completely prevented the cadmium induced fetal growth retardation and anemia. The significance of a possible relationship of small-for-date babies with cigarette smoking and cadmium intake was discussed.     

Behavioral impairment produced by exposure to subclinical amounts of methylmercury chloride.

Rats exposed to small amounts of methylmercury at age 28, 35, and 42 days were impaired in their ability to learn an active avoidance response on tests conducted when they reached adulthood. The amount of methylmercury to which the animals were exposed did not affect food or water intake, body weight, brain weight, or adrenal weight. Adult rats exposed to an equivalent amount of methylmercury did not exhibit behavioral impairment. The data suggest that young organisms are more susceptible to the toxic effects of methylmercury than adults, and that behavioral indices provide a more sensitive index of the toxic effects of methylmercury than clinical indices.     

Changes in hepatic collagen produced by chronic intoxication of rats with ethanol

It was decided to study the effect of chronic intoxication of rats with ethanol on collagen content in the liver, its solubility, and molecular polymorphism. It was found that treatment of rats with 10% ethanol instead of drinking water for 6 months resulted in a 50% increase of collagen content in livers of the investigated animals. Significant changes in quantitative relationships between types I, III, and V collagens were observed. Proportional amounts of type III and V collagens were higher and type I collagen was lower in comparison to those in control rat liver.     

Nonneoplastic effects of vinyl chloride in mouse lung

In a previous study, a high incidence of pulmonary tumors (alveologenic neoplasia in mouse lung exposed to vinyl chloride at heavy dose (2500 and 6000 ppm) for long durations (5 and 6 months) was reported (Y. Suzuki, 1978, Environ. Res.16, 285–301). In the present study, nonneoplastic effects in mouse lung were investigated by light and electron microscopy. As major light microscopic alterations, proliferation and hypertrophy of the terminal bronchiolar cells, consisting of ciliated and Clara cells, hypersecretion of the epithelial mucin in the goblet cells of both the bronchial and the proximal bronchiolar epithelium, hyperplasia of alveolar epithelium, mobilization of alveolar macrophages, and occasional presence of peribronchial or bronchiolar chronic inflammation, were observed. Electron microscopically, Clara cells of the terminal bronchiolar epithelium showed proliferation of the rough and smooth surfaced endoplasmic reticulum and appearance of large and abnormally shaped mitochondria. Similar alterations were found in the ciliated cells. Submicroscopic changes of pulmonary alveoli were represented by focal thickening of the basement membrane, multiple foci of hyperplastic type II cell (the precondition of the alveologenic tumor), active discharge of osmiophilic lamellar bodies from the type II cell and phagocytosis of the bodies by macrophages, appearance of cholesterol crystalloids in the macrophages, degeneration of alveolar septal cells and occasional appearance of a large nucleus with swelling of the capillary endothelium.