Short-term in vitro genotoxicity assays are useful tools to assess whether new and emerging tobacco products potentially have reduced toxicity. We previously demonstrated that potency ranking by benchmark dose (BMD) analysis quantitatively identifies differences among several known carcinogens and toxic chemicals representing different chemical classes found in cigarette smoke. In this study, six whole smoke solution (WSS) samples containing both the particulate and gas phases of tobacco smoke were generated from two commercial cigarette brands under different smoking-machine regimens. Sixty test cigarettes of each brand were machine-smoked according to the International Organization for Standardization (ISO) puffing protocol. In addition, either 60 or 20 test cigarettes of each brand were machine-smoked with the Canadian Intense (CI) puffing protocol. All six WSSs were evaluated in the bacterial reverse mutation (Ames) test using Salmonella typhimurium strains, in the presence or absence of S9 metabolic activation. The resulting S9-mediated mutagenic concentration–responses for the four WSSs from 60 cigarettes were then compared using BMD modelling analysis and the mutagenic potency expressed as number of revertants per μl of the WSS. The quantitative approaches resulted in a similar rank order of mutagenic potency for the Ames test in both TA98 and TA100. Under the conditions of this study, these results indicate that quantitative analysis of the Ames test data can discriminate between the mutagenic potencies of WSSs on the basis of smoking-machine regimen (ISO vs. CI), and cigarette product (differences in smoke chemistry).

中文翻译：

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细菌回复突变试验中全烟液的效力比较分析


短期体外遗传毒性测定是评估新型和新兴烟草产品是否可能降低毒性的有用工具。我们之前证明，通过基准剂量 (BMD) 分析进行效力排名可以定量识别代表香烟烟雾中不同化学类别的几种已知致癌物和有毒化学物质之间的差异。在这项研究中，两个商业卷烟品牌在不同的吸烟机方案下产生了六个含有烟草烟雾颗粒和气相的全烟气溶液（WSS）样品。每个品牌的 60 支测试卷烟根据国际标准化组织 (ISO) 抽吸协议进行机器抽吸。此外，每个品牌的 60 或 20 支测试卷烟均采用加拿大强力 (CI) 抽吸方案进行机器抽吸。在存在或不存在 S9 代谢激活的情况下，使用鼠伤寒沙门氏菌菌株在细菌回复突变 (Ames) 测试中对所有 6 个 WSS 进行了评估。然后使用 BMD 建模分析比较了 60 支香烟的四种 WSS 的 S9 介导的诱变浓度响应，并将诱变效力表示为每 μl WSS 的回复体数量。定量方法在 TA98 和 TA100 中的 Ames 测试中得出了相似的诱变效力排序。在本研究的条件下，这些结果表明，对 Ames 测试数据进行定量分析可以区分基于吸烟机方案（ISO 与 CI）和卷烟产品（烟雾化学差异）的 WSS 的致突变效力。