Cytotoxic effects of trimethyltin chloride on human peripheral blood lymphocytes in vitro.
TL;DR: Trimethyltin chloride was found to induce cytotoxic damage in vitro in human peripheral blood lymphocytes and endoreduplication, an extremely rare spontaneous event in human lymphocytes, was observed in a few cases at all dose levels.
Abstract: Trimethyltin chloride was found to induce cytotoxic damage in vitro in human peripheral blood lymphocytes. Two concentrations (0.5 μg and 1.0 μg) were added to lymphocytes from male and female subj...
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TL;DR: In this article, MeHg binds strongly to protein and soluble sulphydryl groups, which results in catastrophic depolymerization of immature tyrosinated microtubules.
Abstract: Neurotoxicants with similar structural features or common mechanisms of chemical action frequently produce widely divergent neuropathologic outcomes. Methylmercury (MeHg) produces marked cerebellar dysmorphogenesis during critical periods of development. The pathologic picture is characterized by complete architectural disruption of neuronal elements within the cerebellum. MeHg binds strongly to protein and soluble sulphydryl groups. Binding to microtubular -SH groups results in catastrophic depolymerization of immature tyrosinated microtubules. However, more mature acetylated microtubules are resistant to MeHg-induced depolymerization. In contrast to MeHg, the structurally similar organotin trimethyltin (TMT) elicits specific apoptotic destruction of pyramidal neurons in the CA3 region of the hippocampus and in other limbic structures. Expression of the phylogenetically conserved protein stannin is required for development of TMT-induced lesions. Inhibition of expression using antisense oligonucleotides ...
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...Furthermore, TMT impairs immune function, causing splenic atrophy, and altered cell division and cell-cycle kinetics in lymphocytes, resulting in chromosomal alterations and formation of micronuclei (20, 61, 67, 119)....
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TL;DR: The elevation of abnormalities and depression of mitotic index were linear to the increase of donor's age, with a higher frequency in males and females, and individuals with the smoking habit possessed higher frequencies of abnormalities than non-smokers.
Abstract: Spontaneous baseline frequencies of chromosome aberrations, micronucleus counts and cell division were analysed in peripheral lymphocytes of 127 normal healthy individuals in vitro. Cells were subjected to culture for 48 h in serum and PHA supplemented culture medium RPMI 1640. 100 metaphases were observed for chromosome aberrations and 1000 cells each for micronucleus counts and mitotic index. Regression analyses were carried out to see the effect of age on spontaneous abnormalities. The correlation of aberrations, micronucleus formation and mitotic index with donor's age is highly significant. The elevation of abnormalities and depression of mitotic index were linear to the increase of donor's age, with a higher frequency in males. Aged males and females from the age range of 40–70 years showed larger numbers of aberrations. Individuals with the smoking habit possessed higher frequencies of abnormalities than non-smokers.
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TL;DR: Human peripheral blood lymphocytes of healthy male and female individuals of different age groups were treated with two aqueous doses of trimethyltin chloride and Chromatid and chromosome types of aberrations were observed to be increased in both treated sets in all age groups.
33 citations
TL;DR: The clastogenicity of trimethyltin chloride was evaluated in human peripheral blood lymphocytes with micronucleus counts (MNC) as the endpoint and higher frequencies of MNC enhancement were observed in male individuals than in females.
32 citations
TL;DR: The results presented here indicate a considerable toxicological potential of some organotin species but demonstrate clearly that the toxicity is modulated by the cellular uptake capability.
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TL;DR: If human lymphocytes1 or Chinese hamster2 cells are treated with the base analogue 5-bromodeoxyuridine in the latter part of the S period, Giemsa stained chromosomes exhibit a pattern of condensed and extended segments along their length, allowing the identification of the two chromatids, and the observation of sister chromatid exchanges (SCEs) without recourse to autoradiography.
Abstract: IF human lymphocytes1 or Chinese hamster2 cells are treated with the base analogue 5-bromodeoxyuridine (BrdU) in the latter part of the S period, Giemsa stained chromosomes exhibit a pattern of condensed and extended segments along their length. This phenomenon has been attributed to a delay in the spiralisation pattern of the late replicating regions along the chromosomes. Other experiments3 with Chinese hamster ovary (CHO) cells have shown that after two rounds of replication in the presence of BrdU or IdU, sister chromatids stain differentially with Giemsa, allowing the identification of the two chromatids, and the observation of sister chromatid exchanges (SCEs) without recourse to autoradiography. The chromatid with the bifilarly substituted DNA (BrdU substituted in both strands of DNA) is less condensed and stains more weakly with Giemsa than the unifilarly substituted sister chromatid. The yield of SCEs is approximately that observed by autoradiography.
3,159 citations
TL;DR: Failure of the pale stained chromatids to restore Giemsa affinity with urea and trypsin and the diminished Feulgen reaction after light exposure suggest that not masking proteins but photolysis of the BrdU-incorporated chromatid components in the presence of photosensitive dyes play a role in the differential staining.
Abstract: The essential steps of the 33258 Hoechst-Giemsa method for differential chromatid staining consist of (1) 33258 Hoechst treatment, (2) exposure to light, and (3) Giemsa staining. The staining was shown to be a function of the concentration of 33258 Hoechst and the light exposure. The dye was successfully replaced by various metachromatic dyes such as thionine. Two simple methods are proposed. Failure of the pale stained chromatids to restore Giemsa affinity with urea and trypsin and the diminished Feulgen reaction after light exposure suggest that not masking proteins but photolysis of the BrdU-incorporation chromatid components in the present of photosensitive dyes play a role in the differential staining.
280 citations
TL;DR: Male and female Wistar rats were fed bis(tri-n-butyltin)oxide (TBTO) at 0, 5, 20, 80, or 320 mg/kg diet for 4 weeks, and a dose-related reduction was found in the number and staining intensity of TSH-producing cells in the pituitary, correlating with histopathologically decreased activity of the thyroid.
178 citations
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