engleski

Effect of terbuthylazine on human chromatin integrity evaluated by cytome fish assay in vitro

Today approximately 1000 active ingredients with pesticide properties can be found on the market, around 500 are available in EU. Ever wider the presence of agrochemicals in the environment raises concern about their adverse health effects.We tried to evaluate low doses of terbuthylazine (active ingredient/formulation) that are considered safe and likely to occur in residential and occupational exposure (0.00058, 0.0008, 0.008, 25.0 and 156.5
g/ml). Possible clastogenic/aneugenic effects of terbuthylazine active ingredient and formulation were evaluated with and without the use of metabolic activation (S9) on human lymphocytes from 3 donors applying micronucleus assay. To get a better insight into the origin of micronuclei (MN) and other chromatin instabilities, lymphocyte preparations were hybridized using pancentromeric DNA probes. Specificity of genotoxic influence toward A–T base pair rich chromosomes was evaluated by the occurrence of DAPI signals in MN. Active ingredient without S9 significantly induced MN formation in dose dependant manner starting at the 0.0008
g/ml (range 10.3–25.6 vs. control 3–5). Conversely, addition of S9 significantly decreased number of MN compared to untransformed substance. Formulation showed dose dependent increase in number of MN, regardless of S9 (range 8–15). Pure terbuthylazine led to significant occurrence of centromere signals in MN (range 53.3–94.0%) regardless of S9 and DAPI signals with S9 (range 43.5–66.6%). Metabolically activated formulation increased only proportion of centromeric signals (range 50.0–87.5%). Significant occurrence of chromosomes in nuclear buds was observed for treatment with active ingredient (range 16.6– 100%), regardless of S9, while for formulation only with S9 (range 0–50.0%). Nucleoplasmic bridges containing whole chromosomes were observed but considered biologically irrelevant due to their low overall number. Based on higher prevalence of whole chromosomes in MN we can conclude that terbuthylazine has a predominant aneugenic potential, while occurrence of DAPI signals in MN indicates specificity toward 1, 9, 15, 16 and Y chromosomes.

terbuthylazine; cytome FISH assay; lymphocyte

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