Wang Z, Zhou S, Pu X, Klaunig JE (2015) Acrylonitrile Induced Alterations in Mitochondrial Biogenesis and Bioenergetics in Cultured Rat Astrocytes. Int J Cancer Stud Res. 4(3), 75-81. 75 http://scidoc.org/IJCR.php International Journal of Cancer Studies & Research (IJCR) ISSN:2167-9118 Acrylonitrile Induced Alterations in Mitochondrial Biogenesis and Bioenergetics in Cultured Rat Astrocytes Research Article Wang Z, Zhou S * , Pu X, Klaunig JE * Department of Environmental Health, Indiana University School of Public Health, Bloomington, USA. *Corresponding Author: Shaoyu Zhou Ph.D, and James E. Klaunig Ph.D, Department of Environmental Health, Indiana University, 1025 East 7 th street, Bloomington, IN 47405, USA. Tel: 812-856-4936 Fax: 812-856-2445 E-mail: zhous@indiana.edu and jklauni@indiana.edu Received: May 10, 2015 Accepted: June 22, 2015 Published: June 25, 2015 Citation: Wang Z, Zhou S, Pu X, Klaunig JE (2015) Acrylonitrile In- duced Alterations in Mitochondrial Biogenesis and Bioenergetics in Cul- tured Rat Astrocytes. Int J Cancer Stud Res. 4(3), 75-81. Copyright: Zhou S and Klaunig JE © 2015. This is an open-access ar- ticle distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. Introduction Acrylonitrile (ACN) is widely used in the manufacture of acryl- ics, plastics and synthetic rubber. Early investigation suspected that acrylonitrile exposure might possess a risk of causing human brain tumor. For example, epidemiological investigation found that workers in the petrochemical industry and, speciically, in the production of PVC or acrylonitrile-based polymers had an in- creased risk of brain tumor [1]. More studies have found that no increased incidents of brain tumors occurred in workers exposed to ACN [7, 15]. In rodents, however, studies have demonstrated that chronic exposure to acrylonitrile caused dose-related increas- es in brain tumors in rats [2, 12, 24]. Yet, molecular mechanisms behind ACN elicited carcinogenesis in rodents remain largely un- known. Since there is potential human exposure especially among occupational workers, ACN remains an important environmental issue and studies of mechanism of ACN carcinogenesis are of signiicance. Oxidative stress has been proposed to be involved in the mecha- nism of ACN-induced brain tumor in rodents. Our laboratory previously found that ACN treatment resulted in a dose-related increase in oxidative DNA damage in cultured astrocytes as well as in ACN exposed rats. Furthermore, we demonstrated that this ACN induced increase in oxidative DNA damage can be reduced/ prevented by antioxidant supplementation [22, 23]. These results support the involvement of the induction of oxidative stress and damage in the mode of action for acrylonitrile - induced astrocy- tomas in rodents. The role for the mitochondria as a target of environmental agents has been widely implicated into the mechanism of chronic ex- posure to environmental toxicants. Mitochondria are important cellular source of reactive oxygen species (ROS), and on the other side, are susceptible to the attack of chemical induced oxidative stress, which may result in mitochondrial bioenergetics and mito- chondrial genetic alterations that have been frequently observed Abstract Acrylonitrile (ACN) induces brain tumors in rats following chronic exposure. The induction of oxidative stress may be involved in the mechanism of ACN induced carcinogenesis although the exact mechanism remains to be elucidated. The present study was designed to examine whether ACN induces oxidative mitochondrial DNA (mtDNA) damage and al- terations in mitochondrial bioenergetics and biogenesis in cultured rat astrocytes. Cells were treated with ACN for 24 hr, 48 hr, or 14 wk, respectively, to examine the acute and chronic effect of ACN. Oxidative mtDNA damage was detected via measuring 8-hydroxydeoxyguanosine (8-OHdG) with high performance liquid chromatography. mtDNA content was quantitated with real-time PCR, while mitochondrial membrane potential and apoptotic cell death were examined by low cytometry. Astrocytes treated with ACN for 24 hr resulted in a signiicant increase in oxidative mtDNA damage, which was persistent after 14 wk. Similarly, ACN treatment of astrocytes for 24 hr resulted in a dose-dependent increase in mtDNA content, which remained signiicantly increased after 14 wk treatment. In addition, we showed that astrocytes treated with ACN for 14 week exhibited hyperpolarization in mitochondrial membrane potential, suggesting that chronic treatment causes a persistent change in mitochondrial bioenergetics. Furthermore, we demonstrated the cells from chronic ACN treat- ment exhibited resistance to apoptotic cell death induced by doxorubicin and cisplatin. Taken together, these data suggest that ACN treatment induces persistent oxidative mtDNA damage and sustained mitochondrial bioenergetic and biogenic changes, which may be involved in the mechanism of ACN induced carcinogenesis. Keywords: Acrylonitrile; Mitochondrial DNA; Oxidative Stress; Brain Tumor.