Journal of Hazardous Materials 283 (2015) 558–567 Contents lists available at ScienceDirect Journal of Hazardous Materials jo ur nal ho me p ag e: www.elsevier.com/locate/jhazmat miRNA profiling provides insights on adverse effects of Cr(VI) in the midgut tissues of Drosophila melanogaster Swati Chandra a,b , Ashutosh Pandey a , Debapratim Kar Chowdhuri a,∗ a Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow 226001, Uttar Pradesh, India b Academy of Scientific and Innovative Research (AcSIR), New Delhi 110 001, India h i g h l i g h t s • miRNAs were significantly mis-regulated in Cr(VI) fed Drosophila melanogaster. • Majorly altered miRNAs targeted oxidative stress, DNA damage and repair processes. • Mis-regulation of miRNAs was in agreement with their putative target genes. • miRNAs profiling connoted the association of miRNAs in Cr(VI) induced toxicity. • Study further tempts to explore the role of miRNAs in Cr(VI) induced toxicity. a r t i c l e i n f o Article history: Received 18 August 2014 Received in revised form 25 September 2014 Accepted 27 September 2014 Available online 5 October 2014 Keywords: Cr(VI) MicroRNA Microarray DNA damage Drosophila a b s t r a c t Cr(VI), a well-known environmental chemical, is reported to cause various adverse effects on exposed organisms including genomic instability and carcinogenesis. Despite available information on the underlying mechanism of Cr(VI) induced toxicity, studies regarding toxicity modulation by epigenetic mechanisms are limited. It was therefore, hypothesized that the global miRNA profiling in Cr(VI) exposed Drosophila, a genetically tractable model organism, will provide information about mis-regulated miR- NAs along with their targeted genes and relevant processes. Third instar larvae of Drosophila melanogaster (Oregon R + ) were exposed to 5.0–20.0 g/ml of Cr(VI) for 24 and 48 h. Following miRNA profile analy- sis on an Agilent platform, 28 of the 36 differentially expressed miRNAs were found to be significantly mis-regulated targeting major biological processes viz., DNA damage repair, oxidation–reduction pro- cesses, development and differentiation. Down-regulation of mus309 and mus312 under DNA repair, acon to oxidation–reduction and pyd to stress activated MAPK cascade respectively belonging to these gene ontology classes concurrent with up-regulation of dme-miR-314-3p, dme-miR-79-3p and dme-miR-12- 5p confirm their functional involvement against Cr(VI) exposure. These findings assume significance since majority of the target genes in Drosophila have functional homologues in humans. The study fur- ther recommends Drosophila as a model to explore the role of miRNAs in xenobiotic induced toxicity. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Large scale industrial and allied applications of hexavalent Chromium [Cr(VI)], a class IA human carcinogen, positions this Abbreviations: DSBs, double strand breaks; ROS, reactive oxygen species; miRNA, microRNA; DHE, dihydroethidium; SOD, superoxide dismutase; GSTD1, glutathione-S-transferase D1. ∗ Corresponding author at: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India. Tel.: +91 522 2963825/522 2620107x218; fax: +91 522 2628227. E-mail addresses: dkchowdhuri@iitr.res.in, dkarchowdhuri@gmail.com, dkarchowdhuri@rediffmail.com (D.K. Chowdhuri). chemical as one of the major environmental pollutants. Environ- mental presence of Cr(VI) has been reported in different matrices, for example, in soil (66 mg/kg), in ground water (2.03 mg/l) [1], in air (8.40 × 10 -2 g/m 3 ) [2]. Cr(VI) has been reported to cause cyto- toxicity and genotoxicity [3], apoptosis and cell transformation [4]. Recently, it has been reported to cause genomic instability by gen- erating double strand breaks (DSB) in vivo in a genetically tractable model organism, Drosophila, wherein one of the DSB repair path- ways was found to be perturbed [5]. Toxicity onset of Cr depends on the reductive metabolism of Cr(VI). Cr(VI) is rapidly transported to cell by anion transporters and is reduced to trivalent chromium [Cr(III)]. The sequential reduction steps use various antioxidants moieties such as GSH and ascorbate. http://dx.doi.org/10.1016/j.jhazmat.2014.09.054 0304-3894/© 2014 Elsevier B.V. All rights reserved.