Evaluation of toxicity of bisphenol A and derivatives in human prostate normal cell line

Bisphenol A (BPA) is a well-known endocrine disruptor and is widely used in the plastics industry. In recent years, several studies have been conducted on the effects of BPA on male reproductive system. After it was proven that these effects can have serious consequences, use of BPA in many industrial areas has been banned and it has been replaced by its analogues such as bisphenol F (BPF) and bisphenol S (BPS). In this thesis, BPA and its alternatives, namely BPF and BPS were evaluated comperatively for the cytotoxic effects, the genotoxic effects and their potential for causing oxidative stress in immortalized, non-tumorigenic prostatic cells (RWPE-1 cells). In addition, the effects of bisphenol derivatives on DNA repair proteins were evaluated. RWPE-1 cells were incubated with BPA, BPF and BPS for 24 hours at concentrations ranging from 0 to 1000 µM. The inhibitory concentration 50 (IC50) values for BPA, BPF and BPS were found to be 113,74 μM, 249 μM, and 380,90 μM respectively. These results showed that the cytotoxicity potentials were lined up as BPA> BPF> BPS. All cell groups exposed to bisphenol derivatives also showed alterations in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) and levels of glutathione (GSH) and total antioxidant levels (TAOC). Lipid peroxidation levels were not changed. In the standard and modified Comet analysis, all bisphenol derivatives caused significantly increases of DNA damage compared to control groups. All the bisphenol-exposed groups showed decreases in base excision repair (BER) pathway-related proteins, p53 protein levels as well as in DNA repair proteins (OGG1, Ape-1 and MyH). All these data suggest that BPA derivatives can also have both cytotoxic and genotoxic properties. They also alter the expression of DNA repair enzymes. Therefore, further studies are needed to assess whether these substances can be used safely as an alternative to BPA.