Fluoride induces DNA damage and cytotoxicity in human hepatocellular carcinoma cells

Humans are primarily exposed to fluoride (Fl), a widespread environmental pollutant, via contaminated drinking water and foodstuffs. The aim of this study was to examine whether sodium fluoride (NaF) exerted cytotoxic effects in human hepatocarcinoma (HepG2) cells. HepG2 cells were incubated with different concentrations of NaF and reactive oxygen species (ROS) levels, cell cycle, apoptosis, and DNA damage determined. Concentration-dependent studies showed that exposure to HepG2 cells with different concentrations of NaF for 24 hr significantly decreased cell viability and intracellular antioxidant capacity. Furthermore, NaF exposure increased lipid peroxidation levels and accumulation of intracellular ROS; and lowered antioxidant glutathione concentrations. In addition to oxidative impairments, NaF treatment enhanced HepG2 cell death via apoptotic pathway as evidenced by DNA fragmentation and cell cycle arrest. Sodium fluoride treatment unregulated p53 level, and Bax and Bcl2 expression. Diminished cell viability and changes in cell cycle accompanied a rise in p53 expression.     

S-phase,apoptosis and peroxisome proliferation in avian hepatocyte cultures following exposure to the phenoxy herbicide 2,4-D

Phenoxyherbicides induce peroxisome proliferation, as do other structurally related or unrelated chemicals which were found to be nongenotoxic carcinogens in rodents. The widespread use of 2,4-dichlorophenoxyacetic acid (2,4-D) raised concerns over the potential to produce cancer, yet results from epidemiological and experimental studies do not provide definitive evidence that 2,4-D is carcinogenic. The objective of the present study was to verify whether 2,4-D might interfere with cell growth similar to other peroxisome proliferators using cultured avian hepatocytes. Primary hepatocyte cultures from 18-day-old chick embryos were exposed to 2,4-D for up to 72 h followed by an assessment of replicative DNA synthesis and apoptosis. Further, peroxisome proliferation was evaluated. Results showed that 2,4-D stimulated DNA synthesis and suppressed spontaneous apoptosis, while the effects on peroxisome proliferation were less evident.