Toxicity of Harm Reduction Products on Human Development
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Background: Tobacco companies have introduced various types of “harm reduction” products that purportedly help smokers reduce their exposure to carcinogens. However, our lab has demonstrated that such products have other toxicants that impair reproduction. Moreover, our recent work with mouse embryonic stem cells (mESC), which model pre-implantation embryos, showed that mainstream (MS) and sidestream (SS) smoke from harm reduction cigarettes caused as much or more damage than smoke from a traditional brand. Most harm reduction products have not yet been carefully evaluated, and their potential for producing harm, particularly in utero, is unknown. Because direct experimental studies can not be performed on humans in utero, the harm done to human embryos and fetuses by exposure to cigarette smoke is not well characterized. However, prenatal development is extremely sensitive to environmental toxicants, and leading toxicologists agree that the embryo and fetus, rather than adult, should be used to assess the risk of exposure to chemicals including tobacco smoke. Moreover, in utero exposure to toxicants can produce adverse health effects that are manifested months or years after birth. These factors make it very important to develop new technologies for measuring embryotoxicity of environmental chemicals. Our lab is developing embryonic stem cell based assays for evaluating toxicity of tobacco smoke on human prenatal development. In this proposed study, we will compare the toxicity of traditional and harm reduction cigarette smoke for humans. Our assays use human embryonic stem cells (hESC), which provide a unique model for testing environmental toxicants on prenatal stages of human development and thereby perform experiments that would not be possible with actual human embryos. 
 
 
 
 
 
 
 
 Proposed work: We will determine: (1) the differential toxicity of MS and SS smoke from commercially available harm reduction cigarettes and (2) compare the toxicity of the harm reduction brands to a commonly used traditional cigarette using new hESC technology developed in our lab. Our goals will be accomplished by performing experiments using various doses of cigarette smoke to determine the lowest concentrations that produce an effect and the doses that produce a 50% effect. MS and SS smoke from harm reduction cigarettes will be tested using hESC assays that provide endpoints on cell attachment to a matrix, cell division, and cell death. These assays enable important biological processes to be studied in cells that model preimplantation development, and they require relatively short times to perform. The latter point enables rapid collection of data and makes these assays ideal for screening batches of smoke or chemicals for embryotoxicity. Experiments will also be done to determine if the observed effects on hESC can be reversed by washout. Finally, we will co-culture hESC and hepatocytes to determine if liver cells detoxify or enhance the effects of smoke on prenatal development. These data will establish a hierarchy of potency for MS and SS smoke from harm reduction and traditional cigarettes. 
 
 
 
 
 
 Benefits of outcomes: Our data will show the extent to which cells that model human preimplantation embryos are adversely affected by traditional and harm reduction cigarettes and will be useful in evaluating the risks associated with in utero exposure to MS and SS smoke. By heightening awareness of the risks associated with harm reduction smoke, our results could reduce the use of harm reduction products and influence policy and lawmaking on smoking in public places and outdoors. Our hESC assay will open up a new technology that can be used in future evaluations of embryotoxicity of tobacco smoke as well as with other environmental toxicants. Our data will also lead to future identification of the specific chemical toxicants in harm reduction smoke and their molecular targets and will ultimately be important in protecting the reproductive capacity and general health of our population.