Evaluation of in vitro assays for assessing the toxicity of cigarette smoke and smokeless tobacco.
Evaluation of in vitro assays for assessing the toxicity of cigarette smoke and smokeless tobacco.
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DOI：
10.1158/1055-9965.epi-09-0965
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发表时间：
2009-12
期刊：
影响因子：
--
通讯作者：
Shields PG
中科院分区：
文献类型：
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作者：
Johnson MD;Schilz J;Djordjevic MV;Rice JR;Shields PG
烟草和烟草烟雾的体外毒理学研究已被用来了解烟草使用导致癌症的原因，并评估烟草产品设计变化的毒理学影响。鉴于美国食品和药物管理局新近授予烟草制品管理权，要求对烟草制品实施强制性性能标准，并评估制造商的健康声明，因此对毒理学研究的必要性已经提高。本综述的目的是严格评价用于评估烟草制品的与癌症有关的体外毒理学方法，并确定相关的研究空白。PubMed数据库检索用于鉴定自1980年以来发表的与烟草相关的体外毒理学研究。1980年之前发表的具有高度相关性的文章也被确定。收集数据是为了检验：1)研究的目标；2)试验物质的收集方法；3)实验设计；4)毒理学终点；5)与癌症风险的相关性。有多种体外测定方法可用于评估烟草和烟草烟雾，这些方法主要使用非人类细胞模型，以解决不同的作用模式。无烟烟草制品在这些检测中表现不佳。虽然作为定性评估的筛选工具是可靠的，但现有的体外测定法在不同产品的定量比较中得到的验证很差。虽然存在用于非烟草评估的化验电池，但尚未开发出来。将体外研究的数据外推到人类风险仍然是假设的。体外毒理学方法对筛选毒性是有用的，但今天需要更好的方法来监管和评估健康声明。
In vitro toxicology studies of tobacco and tobacco smoke have been used to understand why tobacco use causes cancer and to assess the toxicological impact of tobacco product design changes. The need for toxicology studies has been heightened given that the FDA’s newly granted authority over tobacco products requires mandating performance standards for tobacco products and evaluate manufacturers’ health claims. The goal of this review is to critically evaluate in vitro toxicology methods related to cancer for assessing tobacco products and to identify related research gaps. PubMed database searches were used to identify tobacco-related in vitro toxicology studies published since 1980. Articles published prior to 1980 with high relevance also were identified. The data was compiled to examine: 1) goals of the study; 2) methods for collecting test substances; 3) experimental designs; 4) toxicological endpoints, and; 5) relevance to cancer risk. A variety of in vitro assays are available to assess tobacco and tobacco smoke that address different modes of action, mostly using non-human cell models. Smokeless tobacco products perform poorly in these assays. While reliable as a screening tool for qualitative assessments, the available in vitro assays have been poorly validated for quantitative comparisons of different products. Assay batteries have not been developed, although they exist for non-tobacco assessments. Extrapolating data from in vitro studies to human risks remains hypothetical. In vitro toxicology methods are useful for screening toxicity, but better methods are needed for today’s context of regulation and evaluation of health claims.