Assessment of the genotoxic effects of organophosphorus insecticides phorate and trichlorfon in human lymphocytes

Faculty of Science, Department of Biology, Genetic Toxicology Laboratory, Gazi University, 06500 Teknikokullar, Ankara, Turkey.
Environmental Toxicology (Impact Factor: 3.2). 05/2012; 29(5). DOI: 10.1002/tox.21783
Source: PubMed


In vitro genotoxic effects of organophosphorus insecticides Phorate (PHR) and Trichlorfon (TCF) were investigated using four genotoxicity endpoints. Different concentration ranges between 0.25-2.00 μg mL(-1) of PHR and 2.34-37.50 μg mL(-1) of TCF were applied to lymphocytes. PHR and TCF significantly increased the frequency of chromosomal aberrations (except 2.34 μg mL(-1) for TCF) and sister chromatid exchanges at all treatment times and concentrations. Most of the used concentrations induced a significant increase in the frequency of micronuclei. Furthermore, PHR and TCF significantly decreased the mitotic index at the higher concentrations after 24- and 48-h treatments. In the comet assay, PHR and TCF significantly increased the comet tail at all concentrations. However, the comet tail intensity was significantly increased at only the highest concentration of PHR and at all concentrations of TCF. According to these results, PHR and TCF possess clastogenic, mutagenic, and DNA damaging effects in human lymphocytes in vitro. © 2012 Wiley Periodicals, Inc. Environ Toxicol, 2012.

Download full-text


Available from: Serkan Yilmaz,
59 Reads
  • Source
    • "To determine the safety of medicines and plant products intended for human consumption, systematic toxicological studies must be performed using various experimental models to predict the toxicity and to set the criteria for selecting a safe dose in humans. Genotoxicity tests have been used mainly for the prediction of genotoxicity and carcinogenicity of chemicals because compounds that are positive in these tests have carcinogenic and/or mutagenic potential in humans [13-15]. However, most commonly used herbal formulas have no indications of quality, safety, and efficacy. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Guibi-Tang is a traditional herbal prescription made from 12 different herbs that is used in the treatment of amnesia and poor memory. Methods In the present study, we evaluated the acute oral toxicity and genotoxic potential of Guibi-Tang water extract (GBT) at doses up to 2000 μg/plate an using a bacterial reverse mutation test (Ames test) with Salmonella typhimurium strains TA100, TA1535, TA98, and TA1537, and Escherichia coli strain WP2uvrA. Acute toxicity and genotoxic potential were measured in the presence and absence of an exogenous source of metabolic activation, in an in vitro chromosome aberration assay with Chinese hamster lung (CHL) cells, and in an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Food and Drug Administration. An acute oral toxicity test of GBT was performed in Sprague Dawley rats. The Ames test showed that GBT did not induce gene mutations in S. typhimurium or in E. coli in the presence or absence of S9 activation. Results GBT did not significantly increase the number of structural aberrations in CHL cells with or without S9 activation. The oral administration of GBT at a dose of up to 2000 mg/kg caused no significant increase in the number of micronucleated polychromatic erythrocytes or in the mean ratio of polychromatic to total erythrocytes. Conclusions However, as we did not identify the components of GBT responsible for these effects, other assays are needed to confirm its genotoxicity.
    BMC Complementary and Alternative Medicine 07/2014; 14(1):215. DOI:10.1186/1472-6882-14-215 · 2.02 Impact Factor
  • Source
    • "2.4.2. Alkaline single-cell gel-electrophoresis The comet assay was performed under alkaline conditions according to the original procedure [32] with some modifications [22] [25]. Treated cells were suspended in low melting-point agarose (0.65%) and 75 ␮l of this suspension was quickly layered onto slides previously pre-coated with normal-melting agarose (0.65%). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Clomiphene citrate (CC) is a selective estrogen-receptor modulator that is primarily used to enhance follicular development in women receiving in vitro fertilization (IVF) treatment. Although some studies suggested large increases in ovarian cancer risk related to fertility medications, this association has not been confirmed in other studies. Whether there could be a residual, small risk is still an open question. It is known that genomic instability and multiple genetic changes may be required in carcinogenesis. Genomic instability such as single-base changes, chromosomal rearrangements or aneuploidy may accelerate this process. Genomic instability is not only central to carcinogenesis, but it is also a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease myotonic dystrophy. For these reasons, this study was planned to examine genotoxic effects of CC in human lymphocytes by use of the chromosome aberration (CA) assay, the micronucleus (MN) test, the comet assay, and the test for bacterial mutagenicity in Salmonella typhimurium strains TA98 and TA100 (Ames test). Concentrations of 0.40, 0.80, 1.60, and 3.20μg/ml of CC significantly increased the frequency of chromosomal aberrations (p<0.01 and p<0.001) and micronuclei (p<0.05, p<0.01 and p<0.001) in cultured human lymphocytes, and of DNA damage (tail length, p<0.05, except 0.80μg/ml) in isolated lymphocytes compared with their respective controls. The highest CC concentration at 24h and highest two concentrations after the 48-h treatment significantly decreased the mitotic index. The Ames test showed that the concentrations of CC used in this study induced neither base-pair substitutions nor frame-shift mutations in Salmonella typhimurium strains TA98 and TA100.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 11/2013; 759. DOI:10.1016/j.mrgentox.2013.07.014 · 3.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mutagenic and genotoxic effects of dicapthon were investigated by using the bacterial reverse mutation assay in Salmonella typhimurium TA97, TA98, TA100 and TA102 strains with or without metabolic activation system (S9 mix), and chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) tests in human peripheral blood lymphocytes in vitro. Dicapthon was dissolved in dimethyl sulfoxide for all test systems. 0.1, 1, 10 and 100 μg/plate doses of dicapthon were found to be weakly mutagenic on S. typhimurium TA 98 without S9 mix. The human peripheral lymphocytes were treated with four experimental concentrations of dicapthon (25, 50, 100, and 200 μg/mL) for 24 and 48 h. Dicapthon increased the frequency of SCE only at the 100 μg/mL concentration for the 24 and 48 h applications. Dicapthon also induced abnormal cell frequency, CA/cell ratio and frequency of MN dose dependently for 24 and 48 h. Dicapthon showed a statistically significant cytotoxic effect by decreasing the mitotic index in all concentrations and a cytostatic effect by decreasing nuclear division index in 100 and 200 μg/mL concentrations for both treatment periods when compared with both untreated and solvent controls. These values decreased also in a dose dependent manner.
    Cytotechnology 01/2014; 66(5). DOI:10.1007/s10616-013-9623-x · 1.75 Impact Factor
Show more