Phorate triggers oxidative stress and mitochondrial dysfunction to enhance micronuclei generation and DNA damage in human lymphocytes.

ABSTRACT: Herein, we studied phorate for its toxicological effects in human lymphocytes. Phorate treatment for 3?h has induced significant increase in the lymphocytic DNA damage. Compared to control, comet data from highest concentration of phorate (1000?µM) showed 8.03-fold increase in the Olive tail moment (OTM). Cytokinesis blocked micronucleus (CBMN) assay revealed 6.4-fold increase in binucleated micronucleated (BNMN) cells following the exposure with phorate (200?µM) for 24?h. The nuclear division index (NDI) in phorate (200?µM) treated cells reduced to 1.8 vis-à-vis control cells showed NDI of 1.94. Comparative to untreated control, 60.43% greater DCF fluorescence was quantitated in lymphocytes treated with phorate (500?µM), affirming reactive oxygen species (ROS) generation and oxidative stress. Flow cytometric data of phorate (200?µM) treated lymphocytes showed 81.77% decline in the fluorescence of rhodamine 123 (Rh123) dye, confirming the perturbation of mitochondrial membrane potential (??m). Calf thymus DNA (ct-DNA) treated with phorate (1000?µM) exhibited 2.3-fold higher 8-Hydroxy-2'-deoxyguanosine (8-oxodG) DNA adduct formation, signified the oxidative DNA damage. The alkaline unwinding assay revealed 4.0 and 6.5 ct-DNA strand breaks when treated to phorate and phorate-Cu (II) complex. Overall, the data unequivocally suggests the cyto- and genotoxic potential of phorate in human lymphocytes, which may induce comparable toxicological consequences in persons occupationally or non-occupationally exposed to insecticide phorate.

SUBMITTER: Saquib Q 

PROVIDER: S-EPMC6864401 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature