tailieunhanh - Heavy Metals in the Environment - Chapter 3

Có một nhu cầu cấp thiết để phát triển và thiết lập các cách tiếp cận mới độc tính để đánh giá tác dụng gây độc tế bào và genotoxic tiềm năng của các kim loại nặng có trong môi trường. Trong nhiều thập kỷ qua, rất nhiều trong ống nghiệm và trong thử nghiệm in vivo đã được sử dụng để đánh giá ảnh hưởng của chất gây ô nhiễm môi trường vào các mục tiêu di động của họ. Tăng cường công chúng quan tâm đến những vấn đề này đã tạo ra một nhu cầu cho các. | 3 In Vitro Toxicological Assessment of Heavy Metals and Intracellular Mechanisms of Toxicity Wendy E. Parris and Khosrow Adeli Hospital for Sick Children and University of Toronto Toronto Ontario Canada 1. INTRODUCTION There is an urgent need to develop and establish new toxicological approaches to assess the potential cytotoxic and genotoxic effects of heavy metals found in the environment. In the past several decades numerous in vitro and in vivo assays have been utilized to assess the effects of environmental pollutants on their cellular targets. Increasing public interest in these issues has created a demand for alternatives to using animals in such testing. Bacterial assays are used both for fundamental studies of mutagenesis and for screening of environmental samples as potential genotoxins. Mammalian cell culture systems have also been used in risk evaluation both for investigating mechanisms of chemical carcinogenesis and as bioassay systems for monitoring environmental genotoxins. Isolated cells have been extensively used in toxicological studies in vitro. One organ of particular importance to toxicological research is the liver. The use of in vitro hepatic systems for heavy metal toxicity studies has received increasing attention in recent years. These have been used advantageously in hepatocyte-based cytotoxic- Copyright 2002 Marcel Dekker Inc. ity and genotoxicity assays in vitro. DNA damage in hepatocytes is often measured as covalent DNA adducts or as strand breaks that occur as a result of the DNA repair process. Assessment of DNA damage induced by heavy metals can employ either primary hepatocyte cultures or established hepatic cell lines such as HepG2. The latter cell model provides a convenient and sensitive tool for rapid screening of environmental samples for potential genotoxic and cytotoxic effects. Other recently developed methods for assessing genotoxic effects include use of microarrays that express multiple genes and from which large .