Genetic toxicity assessment using liver cell models: past,present, and future

ABSTRACT

Genotoxic compounds may be detoxified to non-genotoxic metabolites while many pro-carcinogens require metabolic activation to exert their genotoxicity in vivo. Standard genotoxicity assays were developed and utilized for risk assessment for over 40 years. Most of these assays are conducted in metabolically incompetent rodent or human cell lines. Deficient in normal metabolism and relying on exogenous metabolic activation systems, the current in vitro genotoxicity assays often have yielded high false positive rates, which trigger unnecessary and costly in vivo studies. Metabolically active cells such as hepatocytes have been recognized as a promising cell model in predicting genotoxicity of carcinogens in vivo. In recent years, significant advances in tissue culture and biological technologies provided new opportunities for using hepatocytes in genetic toxicology. This review encompasses published studies (both in vitro and in vivo) using hepatocytes for genotoxicity assessment. Findings from both standard and newly developed genotoxicity assays are summarized. Various liver cell models used for genotoxicity assessment are described, including the potential application of advanced liver cell models such as 3D spheroids, organoids, and engineered hepatocytes. An integrated strategy, that includes the use of human-based cells with enhanced biological relevance and throughput, and applying the quantitative analysis of data, may provide an approach for future genotoxicity risk assessment.     

缺血性卒中和短暂性脑缺血发作的二级预防指南的新认识

2006年2月,美国卒中协会主办的国际卒中大会和当月出版的Stroke颁布了新的卒中和短暂性脑缺血发作(transient ischemic attack,TIA)二级预防指南[1,2]。新指南撰写委员会主席、美国哥伦比亚大学Sacco教授强调,与以前的指南[3,4]相比,新指南有了新的改进,它是一个以充分和完整证     

静脉溶栓后冠状动脉再通与室壁瘤形成因素分析

目的分析室壁瘤形成的原因,探讨冠状动脉血管再通与溶拴距发病时间的关系,探讨静脉溶栓治疗的价值。方法接受尿激酶(UK)静脉溶栓治疗的40例首发急性心肌梗死为研究对象,分成冠状动脉再通组22例,未通组18例,通过心脏二维超声检查观察室壁瘤的形成、LVEF及各种严重并发症。溶栓距发病时间分为<6小时、6~12小时两组进行比较。结果室壁瘤再通组占4.5%(1/22),未通组占22%(4/16);溶拴距发病时间<6小时再通组占47.5%(19/40),6~12小时再通组占7.5%(3/40);LVEF再能组0.61±0.11,未通组0.45±0.11;各种严重并发症两组比较差异无显著性意义。结论室壁瘤的产生及LVEF与冠状动脉血管再通的成功与否有关,血管再通的效果与溶栓距发病时间有关。     

模拟舰船磁场与噪声、高温复合对机体作用的方差分析

目的 研究模拟舰船两种剂量水平磁场复合噪声、高温对机体联合作用的特点。方法 采用有交互作用的三因素二水平的正交试验设计方法及方差分析法，按正交表L8（2^7）的要求安排8种复合暴露剂量组合，分别将兔和大鼠分为8个复合暴露组和8个对照组。结果 兔球结膜毛细血管管径、大鼠肝和脾脏HSP70的分析结果显示出磁场是对其影响的主因素（均为P〈0．01），其次是高温（均为P〈0．05）,大鼠下丘脑AVP和大鼠脑组织HSP70的分析结果显示出磁场是对其影响的主因素（均为P〈0．05）。兔血浆内皮素的分析结果显示出磁场与噪声交互作用所对应的F值有非常显著性意义（P〈0．01），磁场与噪声、高温三者之间交互作用所对应的F值也有显著性意义（P〈0．05）。结论 磁场是对上述指标影响的主因素，而高温也是重要因素；磁场与噪声有交互作用，磁场与噪声、高温三者之间也有交互作用；应该重视舰船环境因素对舰船人员的复合作用。     

在膀胱肿瘤并发前列腺增生症患者中采用同次施行膀胱肿瘤切除术和保留尿道粘膜前列腺切除术探讨

目的 探讨膀胱肿瘤并前列腺增生症患者同期施行膀胱肿瘤切除术和保留尿道粘膜前列腺切除术的可行性.方法 对同期施行经尿道膀胱肿瘤切除术及保留尿道粘膜前列腺切除术的16例膀胱癌合并前列腺增生症患者的临床资料进行了回顾性分析.结果 该组患者均顺利康复,无明显合并症,术后复诊,随访时间2～4年,3例出现肿瘤复发.结论 同期施行膀胱肿瘤切除术和保留尿道粘膜前列腺切除术,安全、效果肯定,值得基层医院推广应用.