In vitro genotoxic and cytotoxic effects of some paraben esters on human peripheral lymphocytes.

Parabens (PBs) are p-hydroxybenzoic acid ester compounds commonly employed as antimicrobial preservatives, mainly in food, cosmetic, and pharmaceutical products. The aim of the present study was to investigate the genotoxic and cytotoxic effects of some paraben esters (butyl paraben, propyl paraben, isobutyl paraben, and isopropyl paraben) on human peripheral lymphocytes, using in vitro sister chromatid exchange (SCE), chromosome aberration (CA), and cytokinesis-block micronucleus (CBMN) tests. Lymphocyte cultures were treated with four concentrations of PBs (100, 50, 25 and 10 µg/mL) for 24 and 48 h. Paraben esters significantly induced MN formations as compared to solvent control. Furthermore, butyl paraben and propyl paraben increased MN formations a concentration-dependent manner at 24 and 48 h. PBs increased the CA at 24 and 48 h. However, this increase was not meaningful for butyl paraben and isopropyl paraben at 48 h when compared with solvent control. Butyl, isobutyl, and isopropyl paraben significantly increased the SCE at 24 and 48 h. However, propyl paraben did not induce SCE meaningfully in both treatment periods. A significant decrease in the cytokinesis-block proliferation index and mitotic index was observed in cells exposed to all concentrations of PBs at 24 and 48 h. However, proliferation index was not affected at all concentrations of PBs after 24 h treatment, although it was decreased at the highest concentration of PBs at 48 h. It is concluded that all of the paraben esters used in this study have highly genotoxic and cytotoxic effects on human lymphocytes cells in vitro.

Investigation of genotoxic effects of paraben in cultured human lymphocytes.

Paraben is a phenolic derivative of benzoic acid extensively used as preservatives in food, pharmaceutical, and cosmetic industries due to its antimicrobial characteristics. The objective of this study was to evaluate the in vitro genotoxic effects of paraben in human lymphocyte cultures. Cells were analyzed by cytokinesis-block micronucleus (CBMN), chromosome aberration (CA), sister chromatid exchange (SCE), and comet tests. For CBMN, CA, and SCE assays, the human lymphocytes were isolated from healthy donors and incubated with 500, 250, 100, and 50 µg/mL of paraben for 24 and 48 h, and for comet assay, cells were exposed to 1000, 750, 500, and 250 µg/mL of paraben for an hour. Results showed that numbers of MN and SCEs were not significant in the cells exposed to paraben when compared to the solvent control. However, 500 and 250 µg/mL of paraben induced the CA after 24 h. Also, we observed a significant decrease in the cytokinesis-block proliferation index in cells exposed 250-500 µg/mL paraben for 24 h, and 100, 250, and 500 µg/mL for 48 h. The mitotic index was also decreased at all concentrations and periods. However, the proliferation index was statistically decreased at all concentrations after 48 h treatments. Only the highest concentration of paraben caused DNA migration (mean tail length) in human lymphocytes analyzed by Comet assay. Taken together, results indicated that paraben had cytotoxic effects and caused genotoxicity by affecting directly chromosomes and DNA in human lymphocyte cells in vitro, and may have genotoxic potential for human.

Assessment of in vitro cytotoxic and genotoxic activities of some trimethoprim conjugates.

Trimethoprim, a commonly used antibacterial agent, is widely applied in the treatment of variety of infections in human. A few studies have demonstrated an extensive exposure of man to antibiotics, but there is still a lack of data for cytotoxic effects including nephrotoxicity, gastrointestinal toxicity, hematotoxicity, neurotoxicity and ototoxicity. The main purpose behind this study was to determine cytotoxic and genotoxic activities of trimethoprim (1), trimethoprim with maleic acid (2) and trimethoprim in conjugation with oxalic acid dihydrate (3). The cytotoxic effects of these three conjugates were elucidated by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoium bromide (MTT) assay using embryonic rat fibroblast-like cell line (F2408) and H-ras oncogene activated embryonic rat fibroblast-like cancer cell line (5RP7). Additionally, determination of genotoxic activity of these three compounds were studied by using cytokinesis blocked micronucleus assay (CBMN) in human lymphocytes. The results demonstrated that trimethoprim alone and its combination with other compounds are able to induce both cytotoxic and genotoxic damage on cultured cells (F2408, 5RP7, human lymphocytes).