The mechanism of lead (Pb) modulated heme synthesis pathway induced oxidative stress mediated genotoxicity using standard (ST) and high bioactivation (HB) crosses of Drosophila melanogaster was addressed in the present study. Third instar larvae derived from the ST or HB crosses were reared in sub lethal concentrations of lead acetate (PbAc) treated food media and showed that Pb was readily taken up and accumulated in the said crosses. Pb modulated heme synthesis was evident by significant reductions of δ-aminolevulinic acid dehydratase (δ-ALA-D) and cytochrome P450 (CYP450) and increased accumulation of δ-aminolevulinic acid (δ-ALA). The results have also demonstrated that Pb induced oxidative stress by overproducing reactive oxygen species and lipid peroxidation (LPO) and depletion of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione-s-transferase (GST). Wing somatic mutation and recombination test (SMART) using ST and HB crosses revealed that Pb is mutagenic and weakly recombinogenic. By employing larval hemocytes, there was an increase in percent of tail DNA in alkaline comet compared to that of neutral comet revealing the DNA single strand breaks were the products of Pb modulated heme synthesis pathway induced oxidative free radicals. Based on these findings, it can be concluded that Pb modulated heme synthesis pathway induces oxidative stress that mediates the genotoxicity in D. melanogaster.
KEYWORDS: CYP450, Comet assay, Wing spot test, δ-aminolevulinic acid, δ-aminolevulinic acid dehydratase