Evaluation of possible cytotoxic, genotoxic and epigenotoxic effects of titanium dioxide nanoparticles and possible protective effect of melatonin.

Nanoparticles (NPs) are particles of matter that are between 1 to 100 nm in diameter. They are suggested to cause toxic effects in both humans and environment thorough different mechanisms. However, their toxicity profile may be different from the parent material. Titanium dioxide (TiO) NPs are widely used in cosmetic, pharmaceutical and food industries. As a white pigment, the use of TiO is used in food coloring, industrial paints, clothing and UV filters has increased tremendously in recent years. Melatonin, on the other hand, is a well-known antioxidant and may prevent oxidative stress caused by a variety of different substances, including NPs. In the current study, we aimed to comparatively investigate the effects of normal-sized TiO (220 nm) and nano-sized TiO (21 nm) on cytopathology, cytotoxicity, oxidative damage (lipid peroxidation, protein oxidation and glutathione), genotoxicity (8-hydroxydeoxyguanosine), apoptosis (caspase 3, 8 and 9) and epigenetic alterations (global DNA methylation, H3 acetylation) on 3T3 fibroblast cells. In addition, the possible protective effects of melatonin, which is known to have strong antioxidant effects, against the toxicity of TiO were also evaluated. Study groups were: a. the control group; b. melatonin group; c. TiO group; d. nano-sized TiO group; e. TiO + melatonin group and f. nano-sized TiO + melatonin group. We observed that both normal-sized and nano-sized TiO NPs showed significant toxic effects. However, TiO NPs caused higher DNA damage and global DNA methylation compared to normal-sized TiO whereas normal-sized TiO led to lower H3 acetylation vs. TiO NPs. Melatonin showed partial protective effect against the toxicity caused by TiO NPs.