N-Nitrosocarbofuran, but not Carbofuran, induces apoptosis and cell cycle arrest in CHL cells

Abstract

Carbofuran (CF) is one of the most widely used carbamate pesticides in the world applied for insect and nematode control. Due to its widespread use in agriculture and households, contamination of food, water, and air has become serious, and consequently adverse health effects are inevitable in humans, animals, wildlife and fish. It has been reported that CF alone or in combination with other carbamate insecticides influences the level of reproductive and metabolic hormones such as thyroxine and corticosterone, and results in impairment of endocrine, immune and behavioral functions. In this study, we evaluated the effects of CF and its metabolite, the N-nitroso derivative N-nitrosocarbofuran (NOCF), on genotoxicity, cell growth, cell cycle and apoptosis of Chinese hamster lung fibroblast (CHL) cells. NOCF, but not CF, induced genotoxicity determined by Ames test. NOCF inhibited the growth of Chinese hamster lung fibroblast (CHL) cells with an IC 50 of 12.8 μM. NOCF induced apoptosis of CHL cells, which was demonstrated by morphological changes, DNA fragmentation and flow cytometric analysis. Treatment of CHL cells with NOCF induced significant G 2/M cell cycle arrest. Caspase-3, an executioner of apoptosis was also activated by the treatment of CHL cells with NOCF. These results suggest that NOCF, that is an important metabolite of CF, leads to the induction of cell cycle arrest and apoptosis in CHL cells.