Combined Effects of Lindane and Antibiotics on Tumor Migration and Antioxidant Responses in Drosophila melanogaster.

Organic chlorine pesticides (OCPs) and antibiotics represent persistent organic pollutants and emerging pollutants, respectively. They can coexist in various environmental matrix, while their combined effects were seldom explored. Lindane was chosen to represent OCPs, and sulfamethoxazole (SMX) and tetracycline hydrochloride (TET) were chosen to represent antibiotics. The present study focused on the influences on tumor migration which is essential for both carcinogenesis and cancer treatment and aimed to explore the effects of the binary mixtures on the model organism Drosophila melanogaster. The individual effects showed that lindane significantly enhanced the tumor migration from the eye and brain of the larvae to the ventral nerve cord (VNC) in the concentration range of 40 -100 ng-g-1( P<0.05). SMX enhanced the tumor migration at the highest concentration of 400 ng-g-1, while TET increased the tumor migration from 600 to 1 000 ng-g-1 with a concentration-dependence. The binary mixtures were designed by direct equipartition method. The binary mixtures that contained lindane and SMX or TET significantly enhanced the tumor migration, with a dependence on the lindane-s concentrations. Compared with the predicted effects by independent action (IA) model, the binary mixtures showed synergistic toxicity interactions. Determination on the antioxidant responses showed that, lindane, SMX, TET and the binary mixtures commonly increased reactive oxygen species (ROS) while decreased glutathione (GSH). The effects of binary mixtures containing lindane and SMX on tumor migration were negatively correlated with their influences on catalase (CAT) activities, while such correlation was not observed in the effects of mixtures containing lindane and TET. Such difference was attributed to the different effects of SMX and TET on the antioxidants. Moreover, the effects of binary mixtures containing lindane and SMX, and those containing lindane and TET showed different hierarchical clustering positions. The effects of binary mixtures containing lindane and SMX on tumor migration were closely connected with both ROS and superoxide dismutase (SOD), while those of binary mixtures containing lindane and TET were closely connected with ROS. Such differences supported the attribution to the individual effects of SMX or TET on the antioxidants and also indicated that the antibiotic types can influence the toxicity mechanism of the binary mixtures. [ABSTRACT FROM AUTHOR]