Abstract:Cadmium nitrate decreased the viability of Chinese hamster ovary (CHO) cells in a concentration-dependent manner; 50% inhibition (IC50) was achieved at 0.015 mM. In contrast, lead nitrate appeared to be less toxic. Neither cadmium nitrate nor lead nitrate significantly increased frequencies of binucleated CHO cells with micronuclei (MN). However, both cadmium nitrate and lead nitrate could augment sister chromatid exchanges (SCEs). Cadmium nitrate induced SCEs with a potency approximately equal to that of mito… Show more
“…2). Although differences in the susceptibility of different cells [Lin et al, 1994] and of different organs [Valverde et al, 2002] to lead genotoxicity must be considered, the dose-response for micronuclei reported here in V79 cells coincides surprisingly well with the details of a recent study of micronuclei in the peripheral blood lymphocytes of workers occupationally exposed to lead [Vaglenov et al, 2001]. According to these authors, blood lead levels higher than 1.2 mM may pose an increased genetic risk.…”
Lead compounds are known genotoxicants, principally affecting the integrity of chromosomes. Lead chloride and lead acetate induced concentration-dependent increases in micronucleus frequency in V79 cells, starting at 1.1 microM lead chloride and 0.05 microM lead acetate. The difference between the lead salts, which was expected based on their relative abilities to form complex acetato-cations, was confirmed in an independent experiment. CREST analyses of the micronuclei verified that lead chloride and acetate were predominantly aneugenic (CREST-positive response), which was consistent with the morphology of the micronuclei (larger micronuclei, compared with micronuclei induced by a clastogenic mechanism). The effects of high concentrations of lead salts on the microtubule network of V79 cells were also examined using immunofluorescence staining. The dose effects of these responses were consistent with the cytotoxicity of lead(II), as visualized in the neutral-red uptake assay. In a cell-free system, 20-60 microM lead salts inhibited tubulin assembly dose-dependently. The no-observed-effect concentration of lead(II) in this assay was 10 microM. This inhibitory effect was interpreted as a shift of the assembly/disassembly steady-state toward disassembly, e.g., by reducing the concentration of assembly-competent tubulin dimers. The effects of lead salts on microtubule-associated motor-protein functions were studied using a kinesin-gliding assay that mimics intracellular transport processes in vitro by quantifying the movement of paclitaxel-stabilized microtubules across a kinesin-coated glass surface. There was a dose-dependent effect of lead nitrate on microtubule motility. Lead nitrate affected the gliding velocities of microtubules starting at concentrations above 10 microM and reached half-maximal inhibition of motility at about 50 microM. The processes reported here point to relevant interactions of lead with tubulin and kinesin at low dose levels.
“…2). Although differences in the susceptibility of different cells [Lin et al, 1994] and of different organs [Valverde et al, 2002] to lead genotoxicity must be considered, the dose-response for micronuclei reported here in V79 cells coincides surprisingly well with the details of a recent study of micronuclei in the peripheral blood lymphocytes of workers occupationally exposed to lead [Vaglenov et al, 2001]. According to these authors, blood lead levels higher than 1.2 mM may pose an increased genetic risk.…”
Lead compounds are known genotoxicants, principally affecting the integrity of chromosomes. Lead chloride and lead acetate induced concentration-dependent increases in micronucleus frequency in V79 cells, starting at 1.1 microM lead chloride and 0.05 microM lead acetate. The difference between the lead salts, which was expected based on their relative abilities to form complex acetato-cations, was confirmed in an independent experiment. CREST analyses of the micronuclei verified that lead chloride and acetate were predominantly aneugenic (CREST-positive response), which was consistent with the morphology of the micronuclei (larger micronuclei, compared with micronuclei induced by a clastogenic mechanism). The effects of high concentrations of lead salts on the microtubule network of V79 cells were also examined using immunofluorescence staining. The dose effects of these responses were consistent with the cytotoxicity of lead(II), as visualized in the neutral-red uptake assay. In a cell-free system, 20-60 microM lead salts inhibited tubulin assembly dose-dependently. The no-observed-effect concentration of lead(II) in this assay was 10 microM. This inhibitory effect was interpreted as a shift of the assembly/disassembly steady-state toward disassembly, e.g., by reducing the concentration of assembly-competent tubulin dimers. The effects of lead salts on microtubule-associated motor-protein functions were studied using a kinesin-gliding assay that mimics intracellular transport processes in vitro by quantifying the movement of paclitaxel-stabilized microtubules across a kinesin-coated glass surface. There was a dose-dependent effect of lead nitrate on microtubule motility. Lead nitrate affected the gliding velocities of microtubules starting at concentrations above 10 microM and reached half-maximal inhibition of motility at about 50 microM. The processes reported here point to relevant interactions of lead with tubulin and kinesin at low dose levels.
“…Lead exposure is also known to induce gene mutations and sister chromatid exchanges [201, 202], morphological transformations in cultured rodent cells [203], and to enhance anchorage independence in diploid human fibroblasts [204]. In vitro and in vivo studies indicated that lead compounds cause genetic damage through various indirect mechanisms that include inhibition of DNA synthesis and repair, oxidative damage, and interaction with DNA-binding proteins and tumor suppressor proteins.…”
Heavy metals are naturally occurring elements that have a high atomic weight and a density at least 5 times greater than that of water. Their multiple industrial, domestic, agricultural, medical and technological applications have led to their wide distribution in the environment; raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. They are also classified as human carcinogens (known or probable) according to the U.S. Environmental Protection Agency, and the International Agency for Research on Cancer. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity.
“…Furthermore, although Pb has been classified as a carcinogen by the World Health Organization [23], considerable differences in the genotoxic responses of organisms to Pb have been reported, including no genotoxic responses in some species. Increased sister-chromatid exchanges were detected in Chinese hamster ovary cells exposed to Pb in vivo [24]. Lead-induced chromosomal aberrations were also detected in cultured human leukocytes [25], but not in cultured Chinese hamster cells [26].…”
Abstract-The sensitivity of a freshwater mussel, Anodonta grandis, to DNA damage following lead (Pb) exposure was tested in laboratory and field experiments. Laboratory exposures were conducted for 4 weeks at the following Pb concentrations: 0 (controls), 50, 500, and 5000 g/L. Mussels were also collected from a strip-mine pond contaminated with trace amounts of lead, cadmium (Cd), and zinc (Zn). Significant DNA strand breakage was observed in foot tissue from mussels exposed in the laboratory to the lowest Pb concentration (50 g/L). No evidence of strand breakage was observed in any of the analyzed tissues from the mussels exposed to higher Pb concentrations (500 and 5000 g/L) or from the chronically exposed mussels collected from the strip-mine pond. These data suggest a threshold effect for DNA damage and repair resulting from low-level Pb exposure, whereby repair of DNA strand breaks may occur only if a certain body burden or exposure duration has been achieved.
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