Carbendazim combined with imazalil or cypermethrin potentiate DNA damage in hepatocytes of mice.

D Ðikić, A Mojsović-Cuić, I Cupor, V Benković, A Horvat-Knezević, D Lisicić, N Orsolić

Index: Hum. Exp. Toxicol. 31(5) , 492-505, (2012)

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Abstract

Traces of pesticides imazalil, cypermethrin and carbendazim are detected in plants used for human consumption. To explore whether their application in oral combinations will induce DNA breaks in hepatocytes, a subchronic in vivo experiment was performed in Swiss mice. Doses of 10 mg kg(-1) of imazalil (im) and cypermethrin (cy), and 20 mg kg(-1) of carbendazim (car) and their combinations (im, 10 mg kg(-1) + cy, 10 mg kg(-1); im, 10 mg kg(-1) + car, 20 mg kg(-1); car, 20 mg kg(-1) + cy, 10 mg kg(-1)) were applied daily for 28 days. Afterward, DNA damage in hepatocytes was evaluated by comet assay. Individually, imazalil and cypermethrin damaged DNA at alkali-labile sites, while the tail moment (TM) of carbendazim alone was similar to control but with higher tail length. In combination with carbendazim clastogen, properties of imazalils and cypermethrins were potentiated compared to all other treatments and control. There were pronounced sex differences in pattern of fragmentation between treated groups. Higher long tail nuclei (LTN) in females indicate that certain cells in females were especially prone to total nucleus disintegration. Due to synergistic effects, low environmentally present concentrations of imazalil and cypermethrin in food, and especially their mixtures with carbendazim have genotoxic potential that could be particularly dangerous over prolonged exposure in mammalian organism.