EFFECT OF COMBINATION TREATMENT WITH ANTI-CANCER ALKYLATING DRUGS ON DNA STRUCTURE AND CONDENSATION CONTROLLING ENZYMES

Cisplatin and bleomycin are well recognized DNA-alkylating agents that are widely used in anti-cancer therapy. To overcome complications arising from accumulation of cytotoxic agents in host cells, combination therapy with cisplatin and bleomycin was developed. Cells respond to DNA modifications caused by DNA-alkylating agents with posttranslational ADP-ribose polymerization (PARylation) of DNA and proteins that repair DNA damage, alter gene expression and control the cell cycle. ADP-ribose polymerization of DNA and proteins can induce a network of DNA-protein interactions, broadly changing cellular physiology, responses to DNA damage and outcomes for DNA repair, cell survival, and responses to chemotherapy. This project focuses on investigation of the effect of in vivo treatment with cisplatin and bleomycin on PAR metabolism and structural changes in nuclear DNA and chromatin. The results will help to design combination chemotherapy with decreased dosage of cytotoxic drugs which will prevent their accumulation in host cells and will eliminate side effects.