Aydin O^1,, Akyuz F¹, Tekin N², Burukoglu D³, Ozden H⁴, Ustuner MC⁵, Degirmenci I⁵

Retinoids have a role in the process of chemoprevention. They can inhibit promotion through inhibiting cell proliferation, enhancing apoptosis and anti-oxidative properties. In the present study initiative-p-dimethylaminoazobenzene (p-DAB) and promotive- 2, 3, 7, 8-Tetrachlorodibenzo-p-Dioxin (TCDD) was given to the rats subchronically. It was aim to evaluate the effects on the apoptosis and lipid peroxidation of Retinyl Acetate in the liver and to determine the plasma levels of Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinase-2 (MMP-2) different fixation intervals called as 30, 60, 90 and 120. Apoptosis was determined with assays of Cytochrome c release and DNA fragmentation. Preneoplastic changes in the liver tissues were evaluated histopathologically. In p-DAB+TCDD group there were a decrease apoptosis and an increase lipid peroxidation, VEGF levels and preneoplastic changes beginning from day 60. The increase of MMP-2 levels was shown at day 90 and 120. There was an increase in the apoptosis and also decrease in the lipid peroxidation and levels of VEGF in the Retiniyl Acetate treated rats compare to p-DAB+TCDD group at day 60, 90, and 120. Mild preneoplastic changes and decreased MMP-2 were also observed only at day 120. Retinyl acetate may affect the stages of promotion that appeared preneoplastic changes via inducing apoptosis, reducing lipid peroxidation in the liver and decreasing levels of pro-angiogenic molecule VEGF and pro-invasive molecule MMP-2.

p-dimethylaminoazobenzene, TCDD, chemoprevention, retinyl acetate, liver