Lynch H N, Loftus C T, Cohen J M, Kerper L E, Kennedy E M, Goodman J E
Gradient, 20 University Road, Cambridge, MA 02138, USA.
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, 4225 Roosevelt Way NE, Suite 301 Seattle WA 98105, USA.
Regul Toxicol Pharmacol. 2016 Dec;82:53-93. doi: 10.1016/j.yrtph.2016.10.006. Epub 2016 Oct 17.
Research suggests that exposure to ambient particulate matter (PM) may be associated with lung cancer; however, no mode of action (MoA) for this has been established. We applied a weight-of-evidence (WoE) approach to evaluate recent evidence from four realms of research (controlled human exposure, epidemiology, animal, and in vitro) to determine whether the overall evidence supports one or more MoAs by which PM could cause lung cancer. We evaluated three general MoAs: DNA damage and repair; other genotoxic effects, including mutagenicity and clastogenicity; and gene expression, protein expression, and DNA methylation. After assessing individual study quality, we evaluated the strength of the evidence within as well as across disciplines using a modified set of Bradford Hill considerations. We conclude that the overall WoE indicates it is plausible that PM of various size fractions may cause direct DNA damage, but the evidence is insufficient regarding the alternative MoAs we evaluated. More research is needed to determine whether DNA damage can lead to downstream events and, ultimately, lung cancer.
研究表明，暴露于环境颗粒物（PM）可能与肺癌有关；然而，尚未确定其作用模式（MoA）。我们采用证据权重（WoE）方法来评估来自四个研究领域（人体对照暴露、流行病学、动物和体外研究）的最新证据，以确定总体证据是否支持PM导致肺癌的一种或多种作用模式。我们评估了三种一般作用模式：DNA损伤与修复；其他遗传毒性效应，包括致突变性和染色体断裂效应；以及基因表达、蛋白质表达和DNA甲基化。在评估了各个研究的质量后，我们使用一组经过修改的布拉德福德·希尔因素来评估学科内部以及跨学科的证据强度。我们得出结论，总体证据权重表明，各种粒径的PM可能会导致直接DNA损伤，这似乎是合理的，但对于我们评估的其他作用模式，证据并不充分。需要更多的研究来确定DNA损伤是否会导致下游事件，并最终导致肺癌。
