Introduction Cr(VI)-containing compounds are extensively used in many plating, welding and pigment produc- tion plants. Epidemiological and experimental evi- dence indicates that occupational exposure to Cr(VI) compounds is associated with lung cancer (1-4). Therefore, Cr(VI) is included in the class I of carcino- gens (5). The respiratory tract is considered the prima- ry target organ for Cr(VI) compounds, being the in- halation the main route of entry into human body (1, 2). Cr(III), which is also an essential nutrient in- volved in the metabolism of glucose, insulin and blood Exposure to low levels of hexavalent chromium: target doses and comparative effects on two human pulmonary cell lines Andrea Caglieri 1, 2 , Matteo Goldoni 1, 2 , Giuseppe De Palma 4 , Paola Mozzoni 1, 2 , Simonetta Gemma 3 , Susanna Vichi 3 , Emanuela Testai 3 , Francesca Panico 5 , Massimo Corradi 1 , Sara Tagliaferri 6 , Lucio Guido Costa 6 1 Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Italy; 2 National Institute of Occu- pational Safety and Prevention, Research Centre at the University of Parma, Parma, Italy; 3 Department of Environment & Primary Prevention, Istituto Superiore di Sanità, Rome, Italy; 4 Laboratory of Industrial Hygiene, Department of Experimen- tal and Applied Medicine, University of Brescia, Italy; 5 Section of Respiratory Diseases, Department of Oncology, Haematol- ogy & Pulmonology, University of Modena and Reggio Emilia, Italy; 6 Department of Human Anatomy, Pharmacology and Forensic Medicine, Section of Pharmacology, University of Parma, Parma, Italy Abstract. Intracellular reduction of hexavalent chromium [Cr(VI)] is associated with the production of re- active oxygen species (ROS) and subsequent oxidative damage to different intracellular molecules like DNA, proteins and lipids is believed to contribute to the process of carcinogenesis. Aim of this study was to devel- op a model to establish a relationship between intracellular and macromolecule-bound chromium and some biomarkers of oxidative stress in two in vitro cell lines. Human lung adenocarcinoma (A549) and human bronchial epithelial (BEAS2B) cells were exposed for 3, 8 and 24 hours to relatively low doses (0.5 – 1 – 2 μM) of Cr(VI), i.e., to concentrations similar to what measured and reported by some authors in unexposed subjects and chromate workers. The results show that the differential cytotoxicity of Cr(VI) on the A549 and BEAS2B cell lines may be related both to their different polymorphism of Glutathione S-transferases genes and probably to their unlike permeability to Cr(VI). The glutathione decrease and the induction of HO-1 observed only in BEAS2B cells after Cr(VI) exposure strengthen the idea that glutathione S-transferases ac- tivity may accelerate the reduction of Cr(VI) to Cr(III) with the concomitant induction of oxidative stress. In conclusion, the determination of intracellular Cr in cellular models can be considered an important step in comparing in vitro and in vivo models on the basis of target doses and a promising approach to study the effects of pneumotoxic compounds. (www.actabiomedica.it) Key words: Chromium, oxidative stress, haeme oxigenase, glutathione-S-transferase, BEAS2B cell line O R I G I N A L A R T I C L E ACTA BIOMED 2008; 79; Suppl 1: 104-115 © Mattioli 1885