, 2012) and those reported in the literature (Chen and Moldoveanu, 2003). This confirms that there were no problems with the generation of the test material. The two single blend cigarette types were very similar regarding their construction; e.g., cigarette and tobacco weight, cigarette length, and total alkaloids (data not given). However, due to a reduced filter efficiency and filter ventilation, distinctively higher in their smoke yields than the reference cigarette. Accordingly, the basic chemistry parameters of the single blend cigarettes are comparable and do not point to any differences in the combustion characteristics of these cigarettes. The assay
system responded to CSC in a dose-related manner and, furthermore, was able to discriminate between cigarettes CHIR-99021 mouse with different tobacco fillers. This raises the question of which substances or classes of substances are responsible for the effect on intercellular communication. Polycyclic aromatic hydrocarbons (PAHs), which occur in cigarette smoke, have attracted the special attention of some researchers. PAHs give a considerable response at a concentration of approximately 50 μmol/l in the exposure medium (Upham et al., 2008, Tai et al., 2007, Sharovskaya et al., 2006 and Blaha et al., 2002). Particularly active are those with a bay or bay-like region, e.g., methyl anthracene (Rummel et al., 1999).
Assuming a molecular weight of 250 for the PAHs, this corresponds to 12.5 μg PAHs/ml Sotrastaurin in vivo exposure medium. Assuming further a
delivery of 10 ng PAHs/mg TPM (Roemer et al., 2012 and Ding et al., 2008), then 0.5 ng PAHs were applied with the 0.05 mg TPM/ml in our assay system to obtain a reduction in gap junctions of approximately 50%. Accordingly, the amount of PAHs alone is more than three Non-specific serine/threonine protein kinase orders of magnitude too low to explain the response to TPM. Nitrosated compounds have been identified as actively interfering with intercellular communication (Tiedink et al., 1991). There is also one publication where the carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) has been researched (Lyng et al., 1996). The authors reported that 5 ng NNAL/ml produced a reversible inhibition of intercellular communication. Assuming a delivery of approximately 10 ng NNK/mg TPM or 0.5 ng/0.05 mg TPM applied in our system, this points to a possibly relevant contribution to the effect by this chemical class, especially when considering that other tobacco specific nitrosamines may act in the same direction. However, there are no reports that these results have been reproduced in the same laboratory or by other researchers. Reports on the effect of other smoke constituents, e.g., dioxins (Warngard et al.