Department of Microbiology & Immunology, Wake Forest University School of Medicine, Wake Forest Biotech Place, Winston-Salem, NC 27101, USA.
Regul Toxicol Pharmacol. 2012 Dec;64(3):350-60. doi: 10.1016/j.yrtph.2012.09.004. Epub 2012 Sep 17.
Acute exposure to cigarette smoke or its components triggers diverse cellular effects, including cytotoxicity. However, available data regarding the potential cytotoxic effects of smokeless tobacco (ST) extracts lack consensus. Here, we investigated the relative biological effects of 2S3 reference ST, and whether ST elicits differential cellular/molecular responses compared to combustible tobacco product preparations (TPPs) prepared from 3R4F cigarettes. Total particulate matter (TPM) and whole smoke conditioned medium (WS-CM) were employed as combustible TPPs, while the ST extract was used as non-combustible TPP. HL60, THP1 cells and human PBMCs were used to examine the effects of TPPs in short-term cell culture. Corresponding EC(50) values, normalized for nicotine content of the TPPs, suggest that combustible TPPs induced higher cytotoxicity as follows: WS-CM TPM ≥ ≫ST extract>nicotine. While all three TPPs induced detectable levels of DNA damage and IL8 secretion, the combustible TPPs were significantly more potent than the ST preparation. The major PBMC subsets showed differential cytotoxicity to combustible TPPs as follows: CD4>CD8>monocytes>NK cells. These findings suggest that, relative cytotoxic and other cell biological effects of TPPs are dose-dependent, and that ST extract is the least cytotoxic TPP tested in this study.
急性暴露于香烟烟雾或其成分会引发多种细胞效应，包括细胞毒性。然而，关于无烟气烟草（ST）提取物潜在细胞毒性作用的现有数据缺乏共识。在这里，我们研究了 2S3 参考 ST 的相对生物学效应，以及 ST 是否与来自 3R4F 香烟的可燃烟草产品制剂（TPP）相比引起不同的细胞/分子反应。总颗粒物（TPM）和全烟雾调理培养基（WS-CM）被用作可燃 TPP，而 ST 提取物被用作非可燃 TPP。HL60、THP1 细胞和人 PBMC 用于在短期细胞培养中检查 TPP 的作用。以 TPP 中尼古丁含量为基准归一化的相应 EC(50)值表明，可燃 TPP 诱导的细胞毒性如下：WS-CM TPM≥>>ST 提取物>尼古丁。虽然所有三种 TPP 都诱导了可检测水平的 DNA 损伤和 IL8 分泌，但可燃 TPP 比 ST 制剂更有效。主要的 PBMC 亚群对可燃 TPP 的细胞毒性存在差异，如下所示：CD4>CD8>单核细胞>NK 细胞。这些发现表明，TPP 的相对细胞毒性和其他细胞生物学效应是剂量依赖性的，并且在本研究中测试的 ST 提取物是最不具细胞毒性的 TPP。
