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Toxicological study and genetic basis of BTEX susceptibility in Drosophila melanogaster


Authors:
Temitope Adebambo 1,2,3; Don Fox 2; Adebayo Otitoloju 3

Affiliations:
1) Emory University School of Medicine; 2) Duke University, Durham, NC; 3) University of Lagos, Nigeria

Keywords:
d. apoptosis-induced proliferation; r. stress

Drilling and marketing operations in the oil and gas sector has led to the environmental release of benzene, toluene, ethylbenzene and xylene (BTEX) causing harmful effects to man and other environmental components. Drosophila melanogaster has established protocols that can be used to study the effect of these chemicals and the genome wide mechanism underlying their toxic actions. In this study, the toxicological profile of benzene, toluene, ethylbenzene, p-xylene, m-xylene, and o-xylene in Drosophila melanogaster was evaluated in adult flies and first instar larvae of white w1118 strain. The impact of fixed concentrations of benzene and xylene on apoptosis and mitosis were also investigated in adult progenitor tissues (imaginal discs) found in the third instar larvae. In addition, Genome Wide Association Screening (GWAS) of the Drosophila Genetic Reference Panel (DGRP) was conducted to identify genes that are critical for toxicological responses in Drosophila melanogaster for p-xylene. The results of the toxicity tests showed that toluene and p-xylene are the most toxic chemicals to adult flies with LC50 ≥ 0.166 mM, while a significant and dose-dependent decrease in fly eclosion was observed with benzene, p-xylene, and o-xylene. A significant increase in apoptotic markers and Phospho-Histone-3(PH3) activity was also observed in the imaginal wing discs of larvae exposed to benzene and p-xylene. The genome-wide analyses revealed few single nucleotide polymorphisms (SNPs) with very low p-values (p≤10-5) in 38 regions of Drosophila melanogaster genome as critical for responses to p-xylene. This study reveals the strength of Drosophila melanogaster genetics and apoptotic-proliferative ability of the imaginal disc as an accessible approach to study BTEX compounds.