Mitochondrial Gene Expression, Antioxidant Responses, and Histopathology After Cadmium Exposure Simone Al Kaddissi, 1,2 Alexia Legeay, 2 Antonia Concetta Elia, 3 Patrice Gonzalez, 2 Magali Floriani, 1 Isabelle Cavalie, 1 Jean-Charles Massabuau, 2 Rodolphe Gilbin, 1 Olivier Simon 1 1 Laboratory of Radioecology and Ecotoxicology (LRE), Institute of Radioprotection and Nuclear Safety (IRSN), Bd 186, BP 3, 13115 Saint-Paul-Lez-Durance, France 2 Laboratory of Aquatic Ecotoxicology (EA), University of Bordeaux1/UMR CNRS 5805, Dr Peyneau Square, 33120 Arcachon, France 3 Ecotoxicology Laboratory, Department of Cellular and Environmental Biology, University of Perugia, 06123 Perugia, Italy Received 8 September 2011; revised 27 August 2012; accepted 29 August 2012 ABSTRACT: The present study investigates cadmium effects on the transcription of mitochondrial genes of Procambarus clarkii after acute (0.05, 0.5, and 5 mg Cd/L; 4–10 days) and chronic exposures (10 lg Cd/L; 30–60 days). Transcriptional responses of cox1, atp6, and 12S using quantitative real-time RT-PCR were assessed in gills and hepatopancreas. Additionally, the expression levels of genes involved in detoxi- fication and/or oxidative stress responses [mt, sod(Mn)] and enzymatic activities of antioxidants (SOD, CAT, GPX, and GST) were analyzed. The histopathological effects in hepatopancreas of crayfish were evaluated by light microscopy. Relationships between endpoints at different levels of biological organiza- tion and Cd bioaccumulation were also examined. Cd induced high levels of bioaccumulation, which was followed by mitochondrial dysfunction and histological alterations in both experiments. Moreover, pertur- bations in the defence mechanisms against oxidative stress tended to increase with time. Results also showed that molecular responses can vary depending on the intensity and duration of the chemical stress applied to the organisms and that the study of mt gene expression levels seemed to be the best tool to assess Cd intoxication. # 2012 Wiley Periodicals, Inc. Environ Toxicol 00: 000–000, 2012. Keywords: cadmium; gene expression levels; histology; metallothionein; mitochondria; oxidative stress; crayfish; molecular responses; biomarker; enzymatic activities INTRODUCTION Cadmium (Cd) is present naturally in rivers and lakes at concentrations inferior to 0.1 lg/L and is believed to be one of the most abundant and ubiquitously distributed toxins in the aquatic system (Novelli et al., 2000; Pinot et al., 2000). This trace metal is principally obtained as a by-product in zinc refining (Pinot et al., 2000) and is also found in phos- phate fertilizers (Cupit et al., 2002). It is mainly used in industrial production of batteries, plastic, alloys, and syn- thetic materials (Thornton, 1992). Cd is released to the aquatic environment from both anthropogenic sources, such as industrial and urban effluents agricultural runoffs, and natural sources, such as rocks and soils (Choi et al., 2007). In France, some streams suffer from anthropogenic Cd Correspondence to: O. Simon; e-mail: olivier.simon@irsn.fr Contract grant sponsor: ENVIRHOM research program funded by the Institute of Radioprotection and Nuclear Safety and the CNRS. Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/tox.21817  C 2012 Wiley Periodicals, Inc. 1