E-cigarettes Increase the Risk of Adenoma Formation in Murine Colorectal Cancer Model
- Inouye, Kaili Mika
- Advisor(s): Crotty Alexander, Laura;
- Golden, James
Abstract
Electronic cigarettes (e-cigarettes) are not closely regulated, many e-cigarette liquid compositions contain harmful amounts of nicotine, flavor additives, propylene glycol and vegetable glycerin. E-cigarettes’ effects on the body have been thoroughly researched within the pulmonary system, named as electronic cigarette associated lung injuries (EVALI). However, the effect of e-cigarettes on the gastrointestinal tract is limited and the risk of e-cigarettes on colorectal cancer (CRC) is not known. We used CDX2-Cre-APCmin mice as models for CRC; the murine were used as an in vivo model and stem cell-based 3D organoids were derived from these mice. Previous studies from our group showed that e-cigarette aerosol decreases gut tight junction integrity, increases gut inflammation, and leads to gut leakiness. We tested the effect of e-cigarette vaping on CRC initiation and/or progression. Mice were exposed to e-cigarettes aerosol, then the size and number of polyps were evaluated. The colonic tissue was collected to perform qRT-PCR and to assess the inflammatory cell infiltrate of the epithelium in H&E slides. E-cigarette aerosol exposure resulted in a significant increase in the size and number of polyps found in the CDX2-Cre-APCmin mice compared to the control mice only exposed to air. In vitro studies using stem cells isolated from the CDX2-Cre-APCmin mice showed a higher concentration of CXCL-1 when exposed to e-cigarette and cigarette aerosol compared to cells untreated or exposed to air. In conclusion, e-cigarette vaping could exacerbate CRC initiation and/or progression, by compromising the intestinal barrier integrity and upregulating inflammatory cytokines.