Mitochondrial toxicity and new China goals for TT21C/Adverse Outcome Pathways
作者单位：Evaluation and Research Centre for ToxicologyInstitute of Disease Control and PreventionAcademy of Military Medical Sciences Unilever Safety and Environmental Assurance Centre
会议名称：《中国毒理学会第六届全国毒理学大会》
会议日期：2013年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
基 金：supported by National Key Project on Drug Development from the Ministry of Science and Technology of China(2009ZX09501-034) partly by Unilever International Collaborative Project(CH- 2011-1318)
关 键 词：mitochondrial toxicity toxicity testing risk assessment
摘 要：正Mitochondria are major sources of cellular energy and reactive oxygen species （ROS）,playing fundamental roles in regulation of cell survival and death under pathological conditions. Numerous chemicals have shown to significantly induce mitochondrial toxicity in targeted organ such as liver and *** identification of mitochondrial toxicity for chemicals is important for avoiding hazard exposure in human or environment. However,due to the complexity of mitochondrial toxicity which may involve multiple mechanisms,the assessment of mitochondrial toxicity based on animal test is unsatisfactory. The release of Toxicity Testing in the Twenty-First Century:Vision and A Strategy by the US National Research Council brings new perspectives to the strategy and methods on the assessment of chemical-induced mitochondrial *** development of toxicity testing of mitochondrial toxicity is also transforming expensive and lengthy traditional in vivo animal tests to in vitro high-throughput alternative methods with quantitative parameters analysis and mechanistic exploration. Recently,many in vitro alternative methods have been established for accessing chemical-induced mitochondrial toxicity,such as high content screening,mechanism-based toxicity testing（eg, mitochondrial membrane potential,ATP production, oxygen consumption rate,oxidative phosphorylation, and mitochondrial superoxide generation）. In particular,adverse outcome pathway （AOP）for mitochondrial toxicity is highlighted to get a better mechanistic understanding and in vitro to in vivo *** AOP integrates from chemical characterization to molecular initiating event（MIE）and population response.A significant effort has been made by Chinese scientists to establish and develop Chinese TT21C/*** on previous studies in toxicological alternatives,many new projects have been carried out using TT21C strategies to access toxicitv of various chemicals.