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Using Embryonic Stem Cells as a Novel Model to Compare the Toxicological Effects of Harm Reduction and Conventional Cigarette Smoke on Early Embryo Development


Embryonic stem cells are derived from the inner cell mass (ICM) of blastocysts. Before implantation, cells in the ICM undergo multiple divisions, and after implantation, the entire ICM develops into the embryo. Here, we are interested in the effects of environmental toxicants, such as cigarette smoke, on blastocysts during pre-implantation development. Our lab used mouse and human embryonic stem cells (mESC, hESC) as a pre-implantation model to examine the effects of mainstream (MS) or sidestream (SS) smoke from conventional (Marlboro Red) and harm reduction (Advance Lights, Quest, and Marlboro Lights) cigarettes on early development. Harm reduction tobacco products, contain genetically modified tobacco to produce lower nicotine concentration or are equipped with advanced filters designed to remove carcinogens. These products are often advertised as safer with fewer toxins. In our mESC study, stem cells were cultured in suspension with cigarette smoke solutions and allowed to attach over 24 hours. All brands tested inhibited mESC attachment, survival, and proliferation, and surprisingly, harm reduction cigarette smoke was more potent than conventional smoke (Lin et al., 2009). To further investigate the effects of cigarette products on human embryos, hESC colonies were treated with conventional and harm reduction cigarette smoke solutions for 48 hours. To overcome technical challenges with the hESC system, BioStation technology combined with video bioinformatics tools was used to develop assays based time-lapse video data of dynamic cellular processes (Lin, et al., 2010). This technology was used to quantify hESC colony attachment and growth in various smoke treatments. Data demonstrated that non-cytotoxic doses of conventional and harm reduction cigarette SS smoke impaired hESC colony attachment and growth significantly, but MS smoke did not. Moreover, hESC were more sensitive in most assays than mESC. Most significantly, for both species in all assays, SS smoke from harm reduction cigarettes was more potent than SS smoke from a conventional brand. This study clearly demonstrates the need to monitor harm reduction products carefully and to evaluate both MS and SS smoke emitted from them.

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