In Vitro Genotoxicity of Fipronil Sister Chromatid Exchange, Cytokinesis Block Micronucleus Test, and Comet Assay

Abstract

Fipronil (FP) is a phenylpyrazole pesticide developed by the transnational company Rhône-Poulenc Agro in 1987. Data on the genotoxicity and toxicity of FP are rather inadequate. In this study, we aimed to evaluate the potential genotoxic activity of FP using the single-cell microgel electrophoresis or comet assay, sister chromatid exchanges (SCEs), and micronuclei (MN) in human peripheral blood lymphocytes. In addition, the cytokinesis block proliferation index (CBPI) and proliferation index (PRI) were measured for cytotoxicity. In this study, three different doses of FP were used (0.7, 0.3, 0.1 μg/mL). Mitomycin C (2 μg/mL) and hydrogen peroxide were used as positive controls for SCE MN test systems, and comet assay, respectively. FP induced a statistically significant increase in the MN and SCE frequency and DNA damage in a dose-dependent manner in human peripheral blood lymphocytes (p<0.01, p<0.05, for 0.7 and 0.3 μg/mL, respectively) compared with a negative control. There is no significant difference between 0.1 μg/mL and the negative control for MN frequency, but there is significant difference between all the doses of FP and negative control for SCE frequency, mitotic index, CBPI, and PRI values (p<0.01). Using the alkaline comet assay, we showed that all the doses of the FP induced DNA damage in human peripheral blood lymphocytes in vitro (p<0.05).

Firpronil induced spermotoxicity is associated with oxidative stress, DNA damage and apoptosis in male rats

“…The doses of FPN used were based on a preliminary study conducted in our laboratory (data not shown) and previous studies [23]. Rats were given FPN @ 2.5, 5 and 10 mg/ kg body weight i.e.…”

“…Furthermore, exposure of FPN on in vitro models of different cell lines induces apoptosis, mediated by increased generation of reactive oxygen species, that is, through oxidative stress [21,22]. In addition, FPN induced a statistically significant increase in the micronuclei and sister chromatid exchange frequency and DNA damage in a dose-dependent manner in human peripheral blood lymphocytes [23]. FPN exposure through application on animals as insecticide [24,25] and consumption of different food products containing FPN residues [26,27] indicating risks to human health [28].…”

Increased Sister Chromatid Exchange in Peripheral Blood Lymphocytes from Humans Exposed to Pesticide: Evidence Based on a Meta-analysis

“…200.0μg/ml of Permethrin induced a significant increase in SCE frequency over control values in cultured human lymphocytes (Turkez et al, 2012). Fipronil, a phenylpyrazole pesticide induced a statistically significant increase in the SCE frequency in a dose-dependent manner in human peripheral blood lymphocytes, compared with a negative control (Celik et al, 2014).…”

Persistent phosphorylation at specific H3 serine residues involved in chemical carcinogen‐induced cell transformation

“…In contrast to L02-H3 cells, we observed less DNA fragments in L02-S10A and L02-SSA cells and no obvious change in L02-S28A cells compared to L02-Vector cells. These results suggest that phosphorylation of H3S10 might be associated with regulation of chromosome condensation.To assess whether the status of p-H3S10 affected the degree of DNA damage, we performed cytokinesis-block micronucleus assay (CBMN) in L02 cells treated with 1 μg/mL mitomycin C (MMC), a positive control in CBMN assay for 24 h and measured the frequencies of micronuclei (MN) formation 30. As expected, the frequencies of MN increased in MMC-treated cells by 93.3% compared to control cells treated with a vehicle DMSO.…”