Tetraconazole, a systemic triazole fungicide, shows potential toxic effects in agriculture and human health. Therefore, its cytotoxic effects and accompanying mechanisms should be unraveled. S. pombe (ED666) was used in this study, as a unicellular biology and toxicology model. Cells were grown on standard media and all treatments were done at 30 C and shaking at 180 rpm 1-10 mg/L tetraconazole induced a dose-dependent cell death. Apoptosis was monitored by DAPI ve AO/EB staining. Excessive ROS production and mitochondrial impairment were shown by DCFDA/NBT assays and Rhodamine 123 staining, which were supported by increased expressions of superoxide dismutases and glutathione peroxidase. Involvement of one of the potential apoptotic genes, Cnx1, in apoptosis was shown by increased transcription whereas two other potential genes, Pca1 and Aif1, were not affected by tetraconazole treatment. In conclusion, tetraconazole-induced cytotoxicity and underlying mechanisms which were mediated via ROS damage and mitochondrial dysregulation (Cnx1-driven) were clarified in S. pombe.

Alpha-terpineol, popular monoterpenoid alcohol, is known to cause cytotoxicity in a few cancer cells or to have antioxidant activity, but underlying mechanisms or apoptotic processes in yeast cell death should be understood. We used the fission yeast (Schizosaccharomyces pombe) as a unicellular model to monitor cellular toxicology and physiological mechanisms for the involvement of alpha-terpineol in cell death. Alpha-terpineol caused ROS overproduction and following cytotoxicity and apoptosis in a dose-dependent manner. The effect of oxidative stress was proved using sod1 and sod2 mutants (antioxidant-limited cells), and the results showed that apoptosis was caused by alpha-terpineol-driven oxidation. In addition, resorcinol, a herbal extract from medicinal plants, showed protective activity against alpha-terpineol cytotoxicity. Survival rates, apoptotic cell death ratios, oxidation levels, and antioxidant gene expressions were completely altered; surprisingly sod1 and sod2 levels dramatically increased. However, sod2 was highly upregulated in response to resorcinol treatment with alpha-terpineol. The potential role of the Sod2 enzyme was proved using sod2 mutant cells that do not have a mitochondrial radical-clearing activity. Consequently, the dose-dependent and ROS-mediated cytotoxic/apoptotic effects of alpha-terpineol and the Sod2-dependent protective and antioxidant effects of resorcinol were demonstrated in unicellular model organism S. pombe by this study.