Cytogenetic effects of a mixture of selected metals following subchronic exposure through drinking water in male rats. 2006

S H Jadhav, and S N Sarkar, and H C Tripathit
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243 122, India.

The current study examines the genotoxic effects of subchronic exposure via drinking water to a mixture of eight metals (arsenic, cadmium, lead, mercury, chromium, nickel, manganese and iron) found as contaminants of water sources in different parts of India and its possible association with oxidative stress. Male rats were exposed to the mixture at 0, 1, 10 and 100 times the mode concentration of each metal daily for 90 days. Another dose group at concentration equivalent to maximum permissible limit (MPL) for each metal and a reference group given ip cyclophosphamide were incorporated. The mixture at 100x level significantly increased chromosomal aberrations and micronuclei induction (2.4 folds) in bone marrow cells and reduced the ratio of polychromatic to normochromatic erythrocytes by 25%. The mixture significantly increased sister chromatid exchange in bone marrow (1.67 and 2.3 folds) and spleen (1.57 and 1.98 folds) cells with both 10x and 100x doses. Cyclophosphamide was more potent than the mixture in causing cytogenetic damage in these parameters. In rat spleen, the mixture at 10x and 100x doses caused dose-dependent increase in lipid peroxidation (25.95 and 52.71%) and decrease in the activities of superoxide dismutase (20.36 and 40.62%), catalase (18.24 and 35.50%), glutathione peroxidase (22.33 and 36.12%) and glutathione reductase (19.22 and 31.35%) and in the level of GSH (19.76 and 35.15%). The results suggest that the mixture induced genotoxicity in rat bone marrow and spleen cells at concentrations relatively higher than that found in groundwater sources and the genotoxic effect could relate to induction of oxidative stress. However, observations with lower doses indicate that additive or synergistic interactions following exposure to metal components at MPL levels or at mode concentrations of contemporary groundwater levels in India may not result in clastogenicity in male rats.

UI MeSH Term Description Entries
D008297 Male Males
D008670 Metals Electropositive chemical elements characterized by ductility, malleability, luster, and conductance of heat and electricity. They can replace the hydrogen of an acid and form bases with hydroxyl radicals. (Grant & Hackh's Chemical Dictionary, 5th ed) Metal
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D002374 Catalase An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA. Catalase A,Catalase T,Manganese Catalase,Mn Catalase
D002869 Chromosome Aberrations Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS. Autosome Abnormalities,Cytogenetic Aberrations,Abnormalities, Autosome,Abnormalities, Chromosomal,Abnormalities, Chromosome,Chromosomal Aberrations,Chromosome Abnormalities,Cytogenetic Abnormalities,Aberration, Chromosomal,Aberration, Chromosome,Aberration, Cytogenetic,Aberrations, Chromosomal,Aberrations, Chromosome,Aberrations, Cytogenetic,Abnormalities, Cytogenetic,Abnormality, Autosome,Abnormality, Chromosomal,Abnormality, Chromosome,Abnormality, Cytogenetic,Autosome Abnormality,Chromosomal Aberration,Chromosomal Abnormalities,Chromosomal Abnormality,Chromosome Aberration,Chromosome Abnormality,Cytogenetic Aberration,Cytogenetic Abnormality
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D005979 Glutathione Peroxidase An enzyme catalyzing the oxidation of 2 moles of GLUTATHIONE in the presence of HYDROGEN PEROXIDE to yield oxidized glutathione and water. Cytosolic Glutathione Peroxidase,Glutathione Lipoperoxidase,Selenoglutathione Peroxidase,Glutathione Peroxidase, Cytosolic,Lipoperoxidase, Glutathione,Peroxidase, Glutathione,Peroxidase, Selenoglutathione
D005980 Glutathione Reductase Catalyzes the oxidation of GLUTATHIONE to GLUTATHIONE DISULFIDE in the presence of NADP+. Deficiency in the enzyme is associated with HEMOLYTIC ANEMIA. Formerly listed as EC 1.6.4.2. Glutathione-Disulfide Reductase,Reductase, Glutathione,Reductase, Glutathione-Disulfide
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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