Phorate triggers oxidative stress and mitochondrial dysfunction to enhance micronuclei generation and DNA damage in human lymphocytes.
Saudi J Biol Sci
; 26(7): 1411-1417, 2019 Nov.
Article
in En
| MEDLINE
| ID: mdl-31762602
ABSTRACT
Herein, we studied phorate for its toxicological effects in human lymphocytes. Phorate treatment for 3â¯h has induced significant increase in the lymphocytic DNA damage. Compared to control, comet data from highest concentration of phorate (1000⯵M) 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⯵M) for 24â¯h. The nuclear division index (NDI) in phorate (200⯵M) 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⯵M), affirming reactive oxygen species (ROS) generation and oxidative stress. Flow cytometric data of phorate (200⯵M) treated lymphocytes showed 81.77% decline in the fluorescence of rhodamine 123 (Rh123) dye, confirming the perturbation of mitochondrial membrane potential (ΔΨm). Calf thymus DNA (ct-DNA) treated with phorate (1000⯵M) 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Saudi J Biol Sci
Year:
2019
Document type:
Article
Affiliation country:
Saudi Arabia