Toxic and DNA‐damaging activities of the fungicides mancozeb and thiram (TMTD) on human lymphocytes in vitro

Abstract

The cytotoxic and mutagenic effects of the fungicides mancozeb and thiram were studied using human peripheral blood lymphocytes cultured in vitro with or without an S-9 mix microsomal metabolizing system. The results obtained suggested that the chemicals caused dose-dependent inhibition of thymidine uptake and unscheduled DNA synthesis on both resting and proliferating lymphocytes in the absence of the S-9 mix. In the presence of the S-9 mix, only thiram showed mutagenic activity by eliciting unscheduled DNA synthesis and a significantly higher frequency of sister chromatid exchanges than did controls.

RETRACTED: Mancozeb-induced genotoxicity and apoptosis in cultured human lymphocytes

“…Although, Georgian et al (1983) and Perocco and Santucci (1989) have shown its chromosomal aberration inducing potential in human cells, but these studies are not enough to classify manozeb as a genotoxic agent. Mancozeb exposure can induce genotoxicity and apoptosis in mouse peripheral blood mononuclear cells (PBMC) through reactive oxygen species (ROS) generation (Calviello et al, 2006).…”

Chromosomal aberrations in cultured human lymphocytes treated with the fungicide, Thiram

“…Our data complete previous reports about the effects of Thiram on cultured in vitro lymphocytes evaluated by SCE, MN, and comet assays (Perocco et al, 1989;Pienkowska and Zielenska, 1990;Ardito et al, 1997;Villani et al, 1998). In the SCE and MN analyses performed by Ardito et al (1997), using similar fungicide concentrations, the cytogenetic effects of the Thiram on lymphocytes cultures resulted in being significant also at the lowest concentration of 0.01 μg/mL.…”

“…Several analyses conducted on human lymphocytes showed that treatment with Thiram caused a significant increase of sister chromatid exchanges (SCEs) (Perocco et al, 1989;Pienkowska and Zielenska, 1990;Ardito et al, 1997), unscheduled DNA synthesis (Perocco et al, 1989), and micronuclei formation (Ardito et al, 1997;Villani et al, 1998). Positive results were also obtained when the comet assay test was performed in vitro on cultured human lymphocytes treated with a dose range of 0.1-8.0 µg/mL of Thiram (Villani et al, 1998).…”

Effect of glutathione depletion on apoptosis induced by thiram in Chinese hamster fibroblasts

“…Administration of thiuram disulfides (TDs) to isolated mammalian cells can induce cell death by necrosis [17] or by apoptosis [19,[28][29][30]. Thiram has been also reported to cause cell death in lymphocytes [31] and chondrocytes [32]. However, the knowledge about cellular mechanisms that contribute to thiram-induced apoptosis is still limited.…”