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.     

The Relationship between College Graduate’s Dual Self-Consciousness and Job Search Clarity: The Mediating Role of Perceived Stress

The aim of the study was to explore the relationship between college graduates’ dual self-consciousness, job search clarity and perceived stress, and reveal the mediating role of perceived stress between dual self-consciousness and job search clarity. In this study, 467 college graduates were investigated using the Dual Self-Consciousness Scale, Job Search Clarity Scale, and Perceived Stress Scale. After controlling for gender, age, and region, the results revealed that: (1) private self-consciousness has a significant positive predictive effect on job search clarity; (2) perceived stress has a significant negative predictive effect on job search clarity; (3) perceived stress plays partial mediation effects between private self-consciousness and job search clarity; (4) perceived stress plays complete mediation effects between public self-consciousness and job search clarity; (5) perceived stress has suppressing effects between public self-consciousness and job search clarity.     

(加味)柴芍承气汤对重症急性胰腺炎及其并发症的作用

目的探讨(加味)柴芍承气汤对重症急性胰腺炎(SAP)及其并发症的防治作用。方法65例SAP患者分为中药组35例,对照组30例。2组的内科治疗相同,中药组一经确诊即予柴芍承气汤加味银杏叶治疗,每剂煎成100~150m l,自鼻胃管内注入或口服,每日2~3次,直至患者腹痛缓解、腹胀基本消失、肠鸣恢复。分别观察2组患者治疗72 h后的PaO2、SaO2肾功能、脑病、局部并发症情况、腹痛缓解时间、肠鸣恢复时间、病死率,以及血清中血小板活化因子(PAF)、肿瘤坏死因子(TNF-α)、白介素-1(IL-1)水平变化。结果治疗72 h后中药组与对照组低氧血症的发生率分别为45.71%、73.73%,P<0.05;肾损害、脑病、局部并发症发生率以及病死率均低于对照组,但无统计学差异;腹痛缓解时间、肠鸣恢复时间均优于对照组(P<0.05);中药组血清中PAF、TNF-α、IL-1水平显著降低(P<0.01),而对照组则无明显变化。结论该汤剂对SAP及其并发症有较好的防治作用。抑制细胞因子或炎症介质可能是该汤剂治疗SAP的重要机制。