P-60: Nano-Particle TiO2 Enhances Apoptosis in Testicular Tissue; Evidence for p53, bcl2, cyp19 Genes Expression

Background: Nano-particle Titanium Dioxide (TiO2) is a noncombustible, odorless powder that is widely used in different fields of industries. Previous reports showed that chronic exposure to TiO2 adversely impacts the testicular tissue and down-regulates the antioxidant capacity and down-regulates the endocrine status of the testicles. Present study was designed in order to identify the role of p53, bcl2 in TiO2-induced damages. Moreover, the cyp19 gene expression and its correlation with germinal cells RNA damage in TiO2-exposed animals were evaluated. Materials and Methods: Twenty four mature mice were randomly divided into four groups as control-sham (received 0.3mL normal saline, ip) and test groups including: low dose (10 mg/kg, ip), medium dose (50 mg/kg, ip) and high dose (100mg/kg, ip)-TiO2- received groups. After 35 days, the mRNA and protein levels of bcl2, p53 were assessed by using semi-quantitative RT-PCR and immunohistochemical analyses, respectively. Moreover, the cyp19 mRNA level was assessed by using semi-quantitative RT-PCR. The germinal cells RNA damage was evaluated. Results: TiO2 resulted in a significant increase at p53 mRNA and protein levels and remarkably reduced bcl2 expression, in a dose dependent manner. Moreover, the animals in TiO2-received groups exhibited reduced cyp19 mRNA levels and showed intensively elevated RNA damage in germinal cells. Conclusion: Our data suggest that TiO2 negatively impacts the germinal cells via up-regulating the p53 gene and down-regulating the bcl2 expressions. On the other hand, TiO2 by reducing the cyp19 expression enhances the p53-and bcl2-dependent apoptotic pathways, which in turn result in intensive RNA instability in haploid cells.