Johnson_2021_Toxicol.Rep_8_571

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon (PAH) commonly found in cigarette smoke, automobile exhaust fumes, grilled meat, and smoked food among others. Exposure to B[a]P is associated with a range of toxic effects including developmental, neurological, oxidative, inflammatory, mutagenic, carcinogenic and mortal. Efficient and more affordable experimental models like Drosophila melanogaster could provide more insight into the mechanism of PAH toxicity and help develop new strategies for prevention, diagnosis and treatment of PAH-related conditions. In this study, we examined the induction of some biochemical changes along with mortality and functional senescence by B[a]P and its metabolite, benzo[a]pyrene- 7,8-dihydrodiol-910-epoxide (BPDE) in the Canton-S strain of Drosophila melanogaster, with the aim to establish an alternative assay medium for B[a]P toxicity in flies. Flies were exposed to 2-200 microM of B[a]P and 1-10 microM of BPDE through diet for a seven-day survival assay followed by a four-day treatment to determine the effects of the compounds on negative geotaxis, fecundity and some biochemical parameters of oxidative damage. BPDE significantly reduced the survival rate of flies along the 7 days of exposure whereas B[a]P did not cause any significant change in the survival rate of flies. B[a]P and BPDE significantly reduced the climbing ability of flies after 4 days of exposure. Rate of emergence of flies significantly reduced at 10-200 microM of B[a]P and 5-10 microM of BPDE. Both compounds caused various levels of alterations in the values of reduced glutathione (GSH), total thiol (T-SH), glutathione-S-transferase (GST), catalase (CAT), hydrogen peroxide (H(2)O(2)), nitric oxide (NO) and acetylcholinesterase (AChE) of the flies. The compounds also exhibited high binding affinities and molecular interactions with the active site amino acid residues of Drosophila GST and the inhibitor binding site of Drosophila AChE in an in silico molecular docking analysis, with BPDE forming stable hydrogen bonds with AChE. Hence, the Canton-S strain of Drosophila melanogaster could offer a simple and affordable assay medium to study B[a]P toxicity.