In vitro genotoxic effect of guanosine analogue entecavir

Hepatitis B is a major health problem around the world, and for treatment of this disease many nucleoside anologue drugs received FDA approval are currently used. Entecavir, used in our study, is one of these drugs and there isn?t any studies about it?s genotoxicity in the literature. In the present study, human peripheral lymphocytes were treated with three different concentrations (1.66 µg/ml, 3.33 µg/ml and 6.66 µg/ml) for 24 and 48 hours in vitro to determine the genotoxic effect of entecavir. In the present study, the number of structural chromosomal anomalies and cells with chromosomal anomalies increased in 6,66 µg/ml entecavir concentration for 48 hours treatment period and it was found statistically significant. Also, the mitotic index (MI) decreased in 24 and 48 h treatments and this drop was found higher in 24 h treatments. Besides, it was determined that the effect of entecavir on micronucleus formation was not different from control. Also, entecavir decreased the Nuclear Division Index (NDI) in only 24 h treatment periods significantly. In conclusion, it was seen that the prolonged use of large doses of entecavir lead to genotoxicity and entecavir treated in the first 24 h lead to cytotoxicity, and then cells gained mitotic activity again and continued to divide.