Genoprotective Effects of Amifostine against Mitomycin C-induced Toxicity in Human Hepatoma Cells

Abstract

Mitomycin C is an antitumor antibiotic effective against many human malignancies. Numerous mechanisms have been offered for the anticancer effects of mitomycin C, such as DNA synthesis inhibition, DNA crosslinking and free radical generation. Amifostine is a cytoprotective agent used in cancer chemoprotection, implicating DNAbinding chemotherapeutic agents. The purpose of this study was to discover whether amifostine protects against mitomycin C -induced genotoxicity in HepG2 cells. Furthermore, we measured the DNA damage level with comet assay in HepG2 cells treated with mitomycin C and amifostine in different condition. Besides, we measured the intracellular ROS generation level and GSH levels in cells treated with mitomycin C and amifostine in pre-treatment condition. Our results presented that mitomycin C induced a concernable genotoxic effect in HepG2 cells. Amifostine attenuated the effects of mitomycin C significantly (p<0.0001) by reduction of the level of DNA damage via blocking ROS generation, and improvement of intracellular glutathione levels.