Posters

      Using the Mouse Lymphoma TK Assay to Compare the Mutagenicity of Mainstream Smoke Condensate from Research Cigarettes

      Schramke, H.; Tewes, F. J.; Roemer, E.
      Conference date
      Mar 17, 2002
      Conference name
      Society of Toxicology (SOT) 2002
      Link to more information
      Topic
      Summary

      The mouse lymphoma TK assay -microtiter version- has been established and optimized to quantitatively determine the in vitro genotoxicity of mainstream smoke condensate (MSC) in order to complement our existing testing battery. The assay was validated with the positive control substances methyl methanesulfonate and benzo(a)pyrene and MSC from the reference cigarette 1R4F with and without a metabolic activation consisting of the postmitochondrial (S9) fraction of the livers from rats treated with Aroclor 1254. Reproducible responses -with a coefficient of variation of less than 20%- were found for the positive control substances and for the 1R4F-MSC. To test whether the assay is able to discriminate different cigarette types, MSC from five research cigarettes containing different tobacco blends was prepared and assayed. Positive responses were obtained for all cigarettes, with concentration-related increases in the mutant frequency. To compare the mutagenicity of the cigarettes, the dose-response curve for the mutant frequency was calculated by nonlinear regression analysis. From each dose-response curve, the effective concentration for a 3-fold increase over the spontaneous mutant frequency was calculated and compared. The comparison showed that without S9, the activity of MSC from a 100% burley blend cigarette was lower than that of the other blends; with S9 a similar trend was seen. This is different from the results seen in the S. Typhimurium reverse mutation assay in strains TA98 and TA100 with S9, where the burley cigarette was more active than the 100% bright blend cigarette. This supports the need for a genotoxicity testing battery of complementary assays for the comprehensive testing of cigarette smoke. 

      PMIScience.com is operated by Philip Morris International for the purpose of publishing and disseminating scientific information about Philip Morris International’s efforts in support of its smoke-free product portfolio. This site is a global site for use by scientists, the public health and regulatory communities, and other stakeholders with an interest in tobacco policy. The purpose of this site is not advertising or marketing, nor is it directed at any specific market. It is not intended for use by consumers. New tobacco products sold in the United States are subject to FDA regulation; therefore the content of this site is not intended to make, and nor should it be construed as making, any product related claims in the United States without proper FDA authorization. ​
      ​
      Reduced Risk Products ("RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continuing smoking. PMI has a range of RRPs in various stages of development, scientific assessment and commercialization. All of our RRPs are smoke-free products that deliver nicotine with far lower quantities of harmful and potentially harmful constituents than found in cigarette smoke.