Clastogenic effects of copper sulphate in chick in vivo test system

The clastogenic potential of copper sulphate was evaluated in chicks, employing chromosome aberration (CA) and micronucleus test (MNT) assays. For CA dose, route, time-response and acute vs. subacute studies have been done while only route and dose-response studies were done for MNT. Three different doses were administered intraperitoneally, and only the highest dose was administered per oral. Neonatal chicks were killed after different time intervals. One-fifth of the highest dose was injected repeatedly with a gap of 24 h in-between for sub-acute regimen. A statistically significant (p < 0.05) increase of CA was observed by the two higher doses in i.p. route and by the highest dose in p.o. route. In time-response studies, significant (p < 0.05) results were obtained after 24 and 48 h of exposures. A significant increase in micronucleus counts was also observed with the two higher doses in both bone marrow and peripheral blood erythrocytes by the i.p. route and only by the highest dose in bone marrow erythrocytes by the p.o. route. The present results reveal the genotoxic potential of CuSO₄ in chick in vivo.     

Clastogenic effects of cesium chloride on mouse bone marrow cells in vivo

Clastogenic effects of cesium chloride (CsCl) on mouse bone marrow cells in vivo following oral administration were studied after 24 h. The incidence of chromosome aberrations increased linearly with increasing concentrations of the chemical from 1/20th to 1/5th of the LD50. The frequency of cell division was also enhanced by the lower doses but higher doses were mitostatic. This report is the first on the clastogenicity of cesium on animals.     

Clastogenic activity of strontium chloride on bone marrow cells in vivo

Oral administration of different concentrations of Strontium chloride to laboratory bred mice in vivo induced chromosomal aberrations in bone marrow cell metaphase preparations. The degree of clastogenicity was directly proportional to concentration used at 6, 12, and 24 h of treatment. Duration of treatment could only be related positively in the lower doses. The females showed greater susceptibility than the males at all concentrations used.     

Clastogenic effects of acrylamide in mouse bone marrow cells

Acrylamide, known to induce dominant-lethal mutations (Shelby et al., 1986; Smith et al., 1986) and heritable translocations (Shelby et al., 1987) in rodent germ cells, was hitherto a questionable clastogen in rodent bone marrow (Shiraishi, 1978). Therefore, it was tested for chromosomal aberrations in mouse bone marrow cells, spermatogonia and by the micronucleus test. The intraperitoneally injected doses ranged from 50 to 150 mg/kg. In the chromosomal bone marrow test and the micronucleus assay positive results were obtained with acrylamide, and in the latter test the effect increased linearly with dose. Chromosomal aberrations were not induced in differentiating spermatogonia by the acute acrylamide treatment. Cisplatin was used as a positive control and gave the expected positive response in all 3 tests. The present results demonstrate that acrylamide is no exception among clastogens. It breaks chromosomes not only in mammalian germ cells but also in somatic cells.     

Clastogenic effects of ftorafur. II. Cytogenetic analyses of bone marrow in mice

Our previous work has demonstrated that whereas near-UV radiation is not a mutagen for Haemophilus influenzae cells, it does induce mutations in purified transforming DNA. In order to test various hypotheses concerning this difference, we have irradiated cells at 334 and 365 nm, then lysed them and assayed the DNA for induced mutations and for inactivation of transforming ability. The inactivation was only a little lower than observed with highly purified transforming DNA. The DNA irradiated in vivo was mutated at both wave-lengths, but with considerably lower efficiency than was purified DNA. Neither incubation of the cells after irradiation and before lysis nor freezing and thawing the cells significantly changed the amount of mutation. It is concluded that there is some protection of the DNA against premutational lesions by the in vivo environment, but that it is not enough to account for the total lack of mutation of the cells. A probable explanation of this lack of cell mutation is that lethal lesions in the cells are induced much more readily than premutational lesions.     

Clastogenic effect of the psychotropic drug thioridazine on human chromosomes in vivo

Summary This paper deals with some other population genetic aspects associated with the incidence of a type of primary congenital glaucoma that occurs very frequently in the Gypsy population of Slovakia. In addition to the decreased fertility of affected individuals of Gypsy origin being determined, the relative reproduction fitness and the selection coefficient against this disease were estimated. An increased number of kinship intermarriages in parents of the patients were recorded, namely in the Gypsy group (45.6%). The average inbreeding coefficient for the Gypsy group (F=0.0091) and the non-Gypsy group (F=0.0030) was calculated. Based on the high frequency of primary congenital glaucoma in a relatively small Gypsy subpopulation and on data about their origin, immigration, and settlements in the territory of Slovakia, the authors consider a special case of gene drift—the founder effect—to be the most plausible explanation of the given fact.     

Effects of aluminium salts on bone marrow chromosomes in rats in vivo

Oral administration of aluminium sulphate to laboratory bred Rattus norvegicus for prolonged period induced dose dependent inhibition of dividing cells and an increase in chromosomal aberrations. The effect was not influenced by the duration of exposure. The toxicity of the two salts, aluminium sulphate and potassium aluminium sulphate, did not differ significantly at doses in which the metal contents were kept constant.     

Spindle damaging effect of salbutamol sulphate on bone marrow cells of mice

In vivo assessment and identification of aneuploidy are important phases of genotoxicity evaluation. Considerable effort has been devoted to assess the utility of the existing bioassays and to develop simpler techniques for identifying environmental aneugens. Salbutamol sulphate--an antiasthmatic drug was tested for its spindle damaging effects in bone marrow cells of mice using an in vivo technique, for the evaluation of mitotic index, C-mitotic effects, anaphase reduction and hyperdiploidy. Doses of 0.12, 0.24, 1.2, 2.4, mg/kg body weight were dissolved in bidistilled water and administered intraperitoneally to the mice. Colchicine was taken as positive control for its known aneuploidy-inducing effects. The drug showed positive C-mitotic effects accompanied with increases of mitotic index and decreased frequencies of anaphase in higher doses. Significant levels of hypodiploidy also noted at higher doses. The preliminary results indicated that Salbutamol is capable of inducing C-mitotic effects in mouse bone marrow cells, which is suggestive of possible induction of aneuploidy.     

Cytogenetic effects of acrylamide in the bone marrow of mice

A single i.p. injection of 100 mg/kg acrylamide monomer elevated the frequency of chromosome aberrations and micronucleated polychromatic erythrocytes in the bone marrow of male ICR mice. A positive relationship between frequency of micronuclei and dose of acrylamide was obtained in the dose range of 2 x 25, 2 x 50 and 2 x 100 mg/kg.     

Cytogenetic effects of dacarbazine on mouse bone marrow cells in vivo

The mutagenicity of dacarbazine was assayed in an in vivo test utilizing mouse bone marrow cells. The dose rates used in the experiments were computed according to the standard surface area of the mouse and were proportional to the human dose rate. These were 0.27, 0.44 and 0.60 mg/30 g body weight, each given twice daily at an interval of not less than 6 h. The duration of drug treatment was 24, 48 and 72 h. This alkylating agent proved to be mitodepressive and produced a 3-fold reduction in the mitotic index. The drug also induced chromosome anomalies mainly in the form of chromatid gaps and breaks. These anomalies were proportional to dose rate and duration of drug treatment.     

Clastogenic effects of methylnitrosourea and ethylnitrosourea on chromosomes from human fibroblast cell lines.

Human fibroblast cell lines were pulse-treated for 1 h with either methylnitrosourea (MNU) or ethylnitrosourea (ENU) at various time intervals before harvesting for chromosome analysis. Cells treated with 1 X 10(-3) M, 5 X 10(-4) M, and 1 X 10(-4) M final concentrations of MNU and ENU during the G2 or M phases of the cell cycle showed a significant increase in chromatid-type abnormalities over controls. Cells exposed to MNU or ENU 23 h before harvest showed some chromosome-type abnormalities, reflecting probable damage induced during the G1 phase of the cell cycle or derived from chromatid damage induced during the previous cell cycle. The mitotic indices and incidences of abnormalities suggested a dose response effect when cells were treated with the two higher concentrations and the three concentrations, respectively, of MNU or ENU. Chromatid abnormalities were observed in MUN and ENU-treated cells from each of four cell lines. From this investigation, it was concluded that MNU and ENU treatment of human diploid cell lines in vitro induced both chromatid and chromosome aberrations. MNU and ENU, both of which had previously been shown to be mutagenic in experimental animals, are, therefore, also considered to be mutagenic at the chromosome level in human fibroblasts grown and treated in cell culture.     

Study of the chromosomes in the bone marrow cells of mice inoculated subsequently with various vaccines]

Studies in the effect of a complex of inoculating preparations (poliovaccine, APDD-vaccine, smallpox vaccine, measles vaccine) on dividing cells of bone marrow in mice in line CC57Br showed that a reduction of the interval between introduction of vaccines different in the antigenic respect from 14 days to 4 days results in an increase in frequency of structural chromosomal aberrations 1-2 months after the whole course of inoculations.     

Cytotoxic effects of zirconium oxychloride on bone marrow cells of mice

A single oral administration of an aqueous solution of zirconium oxychloride to mice of both sexes in concentrations $\text{1}\text{20}$, $\text{1}\text{6}$, $\text{1}\text{2}$ of LD₅₀ induced chromosomal abnormalities in bone marrow cells. The frequencies of aberration were directly proportionate to the concentrations used. Female mice were found to be more susceptible than male mice, though not to a significantly higher level. This is the first report on the clastogenicity of this metal.     

Cytotoxic effects of cobalt chloride on mouse bone marrow cells in vivo.

Various dilutions (1/10, 1/20, 1/40) of the lethal toxic dose of cobalt chloride, a non-carcinogenic salt, were found to be clastogenic to bone marrow cells of mice when administered orally in vivo. The clastogenic effects, mainly chromosome breaks, increased significantly with increasing concentration. The frequency of cell division was affected only by higher concentrations of the salt.     

Acute cytogenetic effects of potassium bromate on rat bone marrow cells in vivo

The acute cytogenetic effects of potassium bromate (KBrO3) on rat bone marrow cells in vivo were studied. The incidence of chromosome aberrations in bone marrow cells increased rapidly, reaching a maximum level 12 h after intraperitoneal injection and decreased within 24 h. Dose-response relationships were obtained for both intraperitoneal and oral administrations.     

Acute and subacute cytogenetic effects of the trihalomethanes on rat bone marrow cells in vivo

The mutagenic effects of the trihalomethanes (THMs: chloroform, CHCl3; dichlorobromomethane, CHCl2Br; dibromochloromethane, CHClBr2; bromoform, CHBr3), found in chlorinated drinking water have been studied for their ability to induce chromosome aberrations (CA) in vivo in rat bone marrow cells. THMs were administered intraperitoneally (i.p. acute) and orally (subacute). Using a maximal dose of 1 mmole/kg body weight, positive results were noted for CHCl3, CHCl2Br, CHClBr2 and CHBr3 with i.p. treatment, and for CHCl3 and CHBr3 with oral treatment. The time-dependent increase in CA showed a maximum level at 12 h after i.p. injection and at 18 h after the fifth and last day of oral treatment.     

Clastogenic effect of copper deficiency in cattle

Copper plays an essential role as a micronutrient. Deficiency of this element (hypocuprosis) in experimental and domestic animals has a severe impact on growth as well as on reproduction. The occurrence of lesions during hypocuprosis is correlated with the depletion of an enzymatic group in which copper takes part. The aim of this work was to analyse chromosomal aberrations in Aberdeen Angus cows of the province of Buenos Aires in relation with the Cu plasma levels. Short term lymphocyte cultures were made from samples obtained from four groups of animals: two groups with normal levels of copper in plasma and two groups with severe hypocupremia. This analysis showed a significant increase of the frequency of chromosomal aberrations (p<0.001) in the hypocupremic groups in relation with control groups. Finally, the Spearman correlation analysis showed a significant negative association (p<0.05) between copper levels and the yield of chromosomal aberrations. The increase of the frequencies of chromosomal aberrations found in the hypocupremic groups could be explained by the higher oxidative stress suffered by these animals. A lower catalytic activity of enzymes such as Cu/Zn superoxide dismutase (Cu/Zn-SOD) and cytochrome-c oxidase could increase the intracellular production of active oxygen species (O(2)(-), H(2)O(2) and OH(o)) with the consequent clastogenic effects.