engleski

GENOTOXIC EFFECTS OF ß2-ADRENERGIC AGONISTS ON BACTERIAL TEST SYSTEMS AND HUMAN CELL LINES

In veterinary medicine, ß2-adrenergic agonists are used as bronchodilators and tocolytics but also can be illegally used as growth promoters to improve carcass composition by decreasing fat to the benefit of muscle mass. Earlier studies have reported a range of toxic effects of these substances with signs of acute intoxication in humans and their impact on various metabolic pathways in animals. The aim of this study was to determine the genotoxic and cytotoxic effects of clenbuterol, its metabolite 4-amino-3, 5-dichlorobenzoic acid (4-ADBA) and salbutamol on Salmonella typhimurium, human adenocarcinoma cell line and human peripheral blood lymphocytes as test systems. The range of concentrations of tested substances was set up to cover medicinal, anabolic and NOAEL concentrations. The standard Ames assay conducted on four strains of Salmonella typhimurium showed a mutagenic effect of clenbuterol in a dose of 2500 ng/mL on TA 1537 strain. None of the tested substances had any cytotoxic effect on human adenocarcinoma cell line. The Comet assay conducted on human peripheral blood lymphocytes, in a concentration range of tested substances from 0.8 ng/mL to 2500 ng/mL revealed all tested substances to induce primary damage to genomic DNA by increasing tail intensity. The analysis of chromosome aberrations indicated clenbuterol and salbutamol, when tested in a concentration of 2500 ng/mL, to cause a statistically significant increase in the number of aberrant cells. Study results pointed to genotoxic effect of all tested substances as determined by different methods and on different test systems.

genotoxicity; ß2-adrenegic agonists; bacterial test systems; human cell lines

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