Induction of micronuclei in rat bone marrow after chronic exposure to lead acetate trihydrate.

Lead increasingly contributes to pollution of the environment and may play a role in the development of adverse effects in the human and animal body. Data concerning its mutagenic, clastogenic, and carcinogenic properties have been conflicting. In this study, we evaluated the frequency of micronuclei in bone marrow erythrocytes of rats treated with lead acetate trihydrate. Outbred Wistar rats were exposed to a daily dose of 100 mg/L drinking water for 125 days. The mean value of the total number of micronuclei observed in polychromatic erythrocytes of female rats was significantly higher than that found in the control group (13.375 +/- 2.722 against 9.625 +/- 3.204 micronuclei/1000 cells; P = 0.024 in ANOVA). In exposed female animals, no significant reduction of the ratio of polychromatic to normochromatic erythrocytes was observed (0.990 +/- 0.228 against 1.208 +/- 0.195; P = 0.060 in ANOVA). The effects of lead acetate trihydrate in male rats are both cytotoxic and genotoxic because of a decrease in ratio of polychromatic to normochromatic erythrocytes (0.715 +/- 0.431 against 1.343 +/- 0.306; P = 0.023, ANOVA followed by Tukey test) and an increase in frequency of micronucleated polychromatic erythrocytes (24.167 +/- 7.859 against 4.0 +/- 4.528 micronuclei/1000 cells; P < or = 0.001, ANOVA followed by Tukey test), respectively.

Effect of endosulfan on peripheral sheep leukocytes in vitro.

The immunotoxic and genotoxic effect of endosulfan, an organochlorine insecticide, on sheep peripheral blood leukocytes was examined in in vitro conditions. The immunotoxic effect was evaluated by assays of the metabolic activity of phagocytes and assays for lymphocyte activation--the leucocyte migration-inhibition assay (LMIA) and lympho-proliferation. The significant inhibitory effect of endosulfan on metabolic activity of peripheral blood phagocytes was registered at the actual concentrations of 10(-3)- 10(-4) M. At 10(-3) M the migration of leukocytes was inhibited, both in activated and non-activated with phytohemagglutinin (PHA) leukocyte suspensions (p < 0.01) in LMIA. This indicated the direct cytotoxic effect of endosulfan on the polymorphonuclears and monocytes of which the intensity of migration is an indicator of lymphocyte activation with mitogen. At the concentration of 10(-4) M an immunotoxic effect, ie significant decrease of lymphocyte activation with mitogen was recorded in LMIA. Lympho-proliferation test showed the significant inhibition of proliferation for PHA-stimulated lymphocytes at 10(-3) M and 10(-4) M. Micronucleus assay evaluated the genotoxic potential of endosulfan. Higher concentrations of insecticide (10(-5) M, 10(-6) M) resulted in a significant dose dependent increase in the number of micronuclei.

The importance of lymphocyte micronucleus test for the detection of genotoxic events.

DNA lesion induced by xenobiotics is implemented either through direct interaction of the chemical with DNA through covalent binding or intercalation, or indirectly, through interference with the processes of DNA replication and repair, interaction with proteins, nuclease release from lysosomes etc. The present study emphasizes that the assessment of genotoxic risk arising from xenogenous substances demands the development of sensitive, direct and more exact genotoxic testing methods. One of them is micronucleus assay. It is a simple and quick test for investigating of cytogenic damage with the advantage that exposure to both clastogens and aneugens may be detected.

Effect of chloridazone on the animal organism.

The acute toxic effect of the herbicide chloridazone and mitochondrial respiration were investigated and typical clinical signs of intoxication were described in rats (Wistar), pheasants (Phasianus colchicus) and sheep (Slovak Merino). The LD50 of chloridazone was calculated to be for rats 800 mg/kg bw (range 552 to 1160 mg/kg bw) and for pheasants 3684 mg/kg bw (range 1768 to 7677 mg/kg bw). According to WHO chloridazone is moderately toxic for rats and slightly toxic for pheasants. The LD50 for sheep is 161 mg/kg bw (range 76 to 340 mg/kg bw). Chloridazone thus presents an acute risk for ruminants, which is in coincidence with the WHO classification characterising it as a very toxic compound. The following clinical features of intoxication were observed after p.o. administration of chloridazone: apathy, dyspnoea, hyperventilation, hypersalivation (sheep - foam hypersalivation), paralysis, tonic-clonic convulsions and death in clonic convulsions. Very quick rigor mortis. Chloridazone interfered with mitochondrial respiration in the liver of rats yet its mode of action was different from that of succinate substrate or glutamate-malate. Succinate dependent respiration was significantly decreased in both states (3 and 4) of respiration. Glutamate-malate respiration was not changed in state 4, though it significantly increased in state 3 after ADP administration. RCP (respiration control proportion) value was increased on using either of the substances.