基因芯片技术在金属毒理学中单核苷酸多态性研究的应用

基因芯片这一技术方法在1991年的Science杂志上被首次提出，其高度并行性、高通量、微型化和自动化的特点适应了分析人类基因组计划(human genome project，HGP)所提供的海量的基因序列信息的需要。在毒理学领域，出现了基因组学和生物信息学的一个新分支——毒理基因组学(toxicogenomics)，它从基因组全局上研究毒物作用与基因表达的相互影响。毒理基因组学的最新研究工具就是基因芯片，它可以使我们对成百上千个基因的表达水平同时进行检测。     

基因芯片在毒理基因组学中的应用

毒理基因组学是一门由毒理学与基因组学相互交融而产生的新兴学科。其目的是运用基因组资源及技术探索并研究潜在的威胁人类健康或环境质量的毒物。基因芯片是最主要的基因组资源。通过基因芯片技术 ,可以同时检测成千上万基因的基因表达变化 ,获得高敏感性、可监测的基因水平的毒性标志。本文将对基因芯片的原理及基因芯片在毒理基因组学中的应用作一介绍。     

毒理基因组学及其应用

毒理基因组学是应用基因组学的理论与技术研究组织细胞特定基因的功能，用以评价或预测受试物毒性的一门技术和理论，其研究平台为DNA微阵列技术。毒理基因组学的提出及应用将毒理学推向新的理论和技术发展阶段。本就其在毒理学中的广泛应用及其面临的挑战作一综述。     

毒理蛋白质组学

人类基因组计划的实施导致了基因组学 (genomics)的诞生 ,而其快速推进促使了功能基因组计划的开展 ,使得蛋白质组学 (proteomics)很快成为了一门新兴学科并得到了迅猛发展 ,被人们称为后基因组计划。紧接着 ,基于基因组学和蛋白质组学的战略和技术的边缘与交叉学科纷纷产生 ,毒理基因组学 (toxicogenomics )和毒理蛋白质组学(toxicoprotenomics)就是在基因组计划和后基因组计划的开展中相继诞生和发展起来的 ,并得到了毒理学家和相关学科研究者以及各国政府的重视。1 毒理蛋白质组学的产生 :毒理学 (toxicology)是研究外源性物质对生命有机…     

新书简介

《毒理学》本书共分四部分:第一部分——毒理学的一般原理。介绍了毒物的吸收、分布、代谢、排泄及影响因素和毒理方法的基本概念;第二部分——重点报导毒物在机体内的作用部位,按器官、系统分类。对毒物的作用,组织器官的生理、生化、病理生理等方面的改变作了详细的叙述,第三部分——按照一般的叙述方法介绍了不同类的毒物(如农药、金属、射线,空气污染物、食品添加剂、塑料、动物性毒素、植物性     

美国第21届毒理学会

美国第21届毒理学年会,于一九八二年二月在美国东部波士顿市召开。出席会议的毒理学界人士约二千余人。在这次会议上,宣读和展示的科学论文共675篇。论文的类别概括为十四个方面内容:毒物的转化与分布,吸入毒理学,普通毒理学,金属毒理学,卤代烃化物毒理学,神经毒理学、肿瘤,生化毒理学,环境毒理学,农化物毒理学,免疫毒理学,肾-心血管系统毒理学,致突变等。其中以毒物的转化与分布(占17.6%),吸入毒理学(占14.3%),普通毒理学(占14%)方面的论文为最多。在这次年会上,美国毒理学协会(SOT)举办了二次专题讲座:一、免疫毒理学的基础概念;二、毒理学研究进展(Current Status of Scientific COnsiderations in Conducting Toxicological Research)。会上宣布,第22届全美毒理     

生物芯片分析技术在环境毒理学与环境流行病学研究中的应用

目的生物芯片分析作为新兴的现代毒理学研究技术之一,弥补和克服了传统毒理学的不足,可以快速、高通量地对毒物暴露信息进行处理,并根据毒物暴露信息的差异性分析筛选毒物作用敏感靶目标。生物芯片包括基因芯片、蛋白质芯片、细胞芯片和组织芯片,它们被广泛地应用于生命科学研究及其实践的各个领域。生物芯片的飞速发展推动了环境污染物快速评价技术的发展,改变了传统的环境流行病学评估模式。本文通过分析生物芯片在基因组学、蛋白组学、细胞学及组织分析中的原理及应用,探讨它们在环境毒理学与环境流行病学研究中存在的问题及研究展望。     

毒理学机制研究与"组学"

毒理学机制研究是环境与职业卫生相关疾病控制领域的重要方面。随着科学技术的进步，毒理学机制研究有了较大发展。近年来，“组学”在毒理学机制研究中的应用引起界内学者的普遍关注。“组学”，如基因组学（Genomics）和蛋白质组学（Pmteomics），是生命科学的前沿，具有以“通量化”的优势，但同时具有局限性，不仅在检测成本、定量、标准化等方面尚需完善，在能否回答基因间精细关系等科学问题方面也存在明显的不足。针对某些情况下“组学”概念及技术被不恰当使用的问题，Pognan曾尖锐地指出：基因组学，蛋白质学，毒理代谢组学，希望不是“时髦组学”。     

微阵列技术在毒理学研究中的应用

毒理基因组学是一门研究与环境因素所致健康危险性有关的人类基因组的新学科。这是毒理学和基因组技术结合所产生的一门新的学科分技。微阵列技术即基因芯片技术包括芯片制备、待检样品制备、探针杂交、检测和数据处理。微阵列技术在毒理学主要应用于可疑毒物的鉴定、作用机制的研究、剂量-反应关系的评价、化学混合物中交互反应的鉴定、暴露的生物标记和易感性的生物标记。例如微阵列技术已用于研究人膀胱癌的生物标记以及氯化镉、苯并（a）芘和三氯乙烯相关基因调控的指纹。还介绍了一种全自动、多用途、新型的分子生物学工作站NanoChip分子生物系统。     

水生生态毒理学方法在环境卫生研究中的应用

水生生态毒理(aquatic ecotoxicology)系采用水生生物为试验对象进行毒理学研究，是水生毒理学、环境毒理学及环境生物学的重要组成部分，可为水质、生物毒素评价及制订各种水质标准(包括渔业水质标准、排放标准等)提供科学依据，在环境卫生研究中起着重要作用。在国内外，对水生生态毒理学的一些方法进行标准化，如ISO(国际标准组织)已向各国推荐了一些标准方法，国家环境保护局也相应的制定了标准，及国家标准。生态毒理其范围包括水体中主要生物类群中代表性生物的毒性试验，如游泳性生物代表鱼类毒性试验：浮游动物代表水蚤类毒性试验：浮游植物代表藻类毒性试验；原生动物代表梨形四膜虫毒性试验；甲壳动物代表虾毒性试验；贝类代表贻贝及毛蚶毒性试验；以及这些代表性生物的富集试验、致突变试验、长效应试验和各级水生食物链生物对毒物的迁移转化等。     

卫生毒理学实验教学方法探讨

目的：探讨如何加强卫生毒理学的实验教学。方法：针对卫生毒理学这门课程的特点及在预防医学领域中的作用和意义,着重阐述了加强卫生毒理学实验教学的重要性,以及加强实验课程教学的一些方法和措施。结论：通过多种方法和措施使实验课程教学取得了较好的效果。     

Implications of gender differences for human health risk assessment and toxicology

This paper from The Human Health working group of SGOMSEC 16 examines a broad range of issues on gender effects in toxicology. Gender differences in toxicology begin at the gamete and embryo stage, continuing through development and maturation and into old age. Sex influences exposure, toxicokinetics, and toxicodynamics. The effects of sex have often been overlooked in both epidemiology and toxicology. In addition to the obvious modifying effects of the sex hormones and conditions affecting the male and female reproductive organs and sex roles, both genetic and hormonal effects influence many aspects of life and toxic responses. All aspects of toxicology should consider gender-balanced designs so that a more comprehensive understanding of differences and similarities can be obtained. Differential gene expression is a new frontier in toxicology. Risk assessment should account for gender and life cycle differences. The biological basis for altered sex ratios observed in several populations should be sought in animal models, and expanded to other compounds that might exert sex-selective effects. Wherever possible and feasible, toxicologic and environmental epidemiological studies should be designed and have sufficient statistical power to quantify differential gender-based exposures and outcomes.     

TOXNET: A computerized collection of toxicological and environmental health information

The Toxicology and Environmental Health Information Program, managed by the National Library of Medicine's Division of Specialized Information Services, provides access to a number of online bibliographic and factual computer files concerned with the toxicology, safety and handling, and environmental fate of chemicals, along with other files that cover genetic toxicology, developmental and reproductive toxicology, mutagenesis, carcinogenesis and toxic chemical releases.     

毒理学发展的新方向——系统毒理学

伴随着系统生物学和高通量分子检测技术的发展,系统毒理学渐显端倪.系统毒理学是指通过整合分子、细胞、组织等不同研究层次的高通量信息,系统研究外源性化学物和环境应激等与机体的相互作用的一门学科.该文综述了系统毒理学的诞生背景、研究策略、研究技术及其主要应用,如研究毒物作用分子机制等.尽管还有不足之处,系统毒理学的发展和应用有望对人类的环境与健康研究,如阐明污染物的健康损害机制等,产生推动作用.     

Twenty-five years of behavioral toxicology within occupational medicine: a personal account

Decisive for my long-term involvement in behavioral toxicology were the hours spent in interviewing and testing patients with occupational poisonings during the first years of my career as a clinical psychologist within the framework of occupational medicine. Important auxiliary factors were the innovative and inspiring scientific climate at our Institute, and the supportive kind of scientific education provided by this environment during the years. It has been rewarding and exciting to follow the international progress of behavioral toxicology. Advances in this special domain of research were and are partly related to advances in occupational epidemiology and toxicology, in neurotoxicology and other allied disciplines, as well as to advances in other branches of psychology. But the major challenge to behavioral toxicology during the first decades of its existence has been finding its place and role within these disciplines. Important challenges for the next decades are defining further the exposure-effect relationships as a basis for the standard setting, extending the surveillance of neurotoxic hazards to the developing countries, and searching for better understanding of the practical significance o neurobehavioral effects, eg, from the point of view of the afflicted individual. To realize these aims, further efforts are needed to coordinate the field of behavioral toxicology and to augment communication between those immediately involved.     

预防医学专业毒理学实验教学过程中的实践改革与探索

目的通过一系列毒理学实验教学实践与改革措施,以提高毒理学的教学质量与教学效果。方法从毒理学实验教学过程中的常见问题及薄弱环节入手,采用预防医学专业本科生与毒理学实验教师互动的综合实验教学模式,并对毒理学实验教学实践改革的效果进行评价与改进。结果学生学习毒理学的兴趣得以提高,培养了学生的科学创新思维,提高了学生的实验动手能力、观察与独立思考能力、搜集、处理实验数据及撰写实验报告的能力。结论综合式毒理学实验教学模式得到了学生的肯定,教学质量也得到了相应的提高,获得了一定的教学效果。     

美国毒理学信息规划概况

美国从1967年开始实施毒理学信息规划.该规划的目的是建立有关毒理学数据库,到目前为止已建有十几人在全球有影响的数据库.这些数据库涉及到毒理学的各种领域,为毒理学研究提供参考信息以及为用户提供查询服务.本文对有关的数据库作了简要介绍.     

Drugs and firearm deaths in New York City, 1990–1998

Firearm deaths remain among the leading causes of mortality in the United States. Changing law enforcement activities, incarceration, drug use, and socioeconomic conditions may have played roles in the declining rates of firearm deaths during the 1990s. Using records from the Office of the Chief Medical Examiner, we analyzed the role of drugs in firearm deaths in New York City between 1990 and 1998. Positive drug toxicology was present in over half of all firearm death victims during this time. Cocaine, cannabis, opiates, and alcohol accounted for almost all of these deaths with drug-positive toxicology. There were decreases in cocaine- and alcohol-positive toxicology for firearm deaths in New York City starting in the early 1990s; there was a more gradual decrease in heroin-positive toxicology for firearm deaths. Cannabis-positive toxicology for firearm deaths increased in the early part of the 1990s and then decreased starting in the mid-1990s. Although the disparities between minority and white firearm death rates narrowed during this time, minorities remained about three times more likely to be victims of fatal firearm violence than whites in 1998. The highest firearm death rates were among African American and Latino male decedents, with a larger proportion of Latinos testing cocaine or opiate positive, while a larger proportion of African Americans tested cannabis positive. These results suggest a complex role of drugs in firearm-related deaths.     

One century of studies on lead poisoning in papers published in La Medicina del Lavoro

One century of papers published in the Italian journal of occupational medicine, La Medicina del Lavoro, shows clearly that the study of lead is an exemplary topic for occupational physicians, enabling them to observe the evolution of research in the field of occupational health. The numerous pathological features of lead poisoning, doctors' successive therapeutic responses, and their gradual development of preventive techniques, form a paradigm that has subsequently been applied to all other fields of industrial toxicology. The evolution of the study of lead poisoning during this century is a complete example in the field of occupational toxicology for medical students: it will stimulate them in applying both clinical and preventive knowledge in the field of industrial toxicology.     

Could pesticide toxicology studies be more relevant to occupational risk assessment?

Pesticide toxicology study design has evolved from concern for oral exposure via food residues. The emphasis on the oral route does not generally apply to workers that are exposed primarily via the dermal route either handling pesticides or re-entering treated fields. As a result numerous assumptions about how oral toxicology results relate to dermal exposure must be made when conducting worker risk assessments. These assumptions introduce a high degree of uncertainty. Alternative toxicology study designs are suggested to reduce uncertainty when assessing risk. Because the dermal route is so important to characterizing occupational risk, methods to improve the accuracy of dermal absorption estimates are suggested, including the use of human subjects to study dermal absorption. Additional suggestions include tailoring dermal, oral and inhalation kinetic study designs to reflect worker exposure dosages. Suggestions are made to routinely conduct a single dose toxicity study patterned after the neurotoxicity study design to distinguish single dose effects and NOAELs from those resulting from multiple doses. Finally, interspecies pharmacokinetics studies are proposed to determine which toxicology study regimen of dosing best reflects intermittent worker exposure.