Clinical Investigations on Human Health Responses to Thirdhand Smoke and Electronic Cigarette Exposure
Abstract
Abstract of the Dissertation
Clinical Investigations on Human Health Responses to Thirdhand Smoke and Electronic Cigarette Exposure by Shane Sakamaki-Ching Doctor of Philosophy, Graduate Program in Cell, Molecular, and Developmental Biology University of California, Riverside, March 2022 Dr. Prue Talbot, Chairperson
Background: Cigarette smoking causes diseases such as cancer, heart disease, and stroke. The diseases associated with electronic cigarettes (ECs) are not as well understood. Cigarette smoking leaves a residue, thirdhand smoke (THS), on indoor surfaces. The health effects of THS on humans is limited to one study. Our purposes were to: (1) identify urinary biomarkers of potential harm and exposure and correlate these to metal concentrations in urine from cigarette smokers and EC users; (2) determine the responses of humans dermally exposed to THS; and (3) identify molecular changes in keratinocytes exposed to THS extract.
Methods: In Chapter 1, urine from non-smokers, EC users, and cigarette smokers was evaluated for biomarkers of exposure, effect, and potential harm. In Chapter 2, human participants were exposed dermally to clothing impregnated with filtered clean air or THS; their urine was analyzed for biomarkers of exposure and harm, and their plasma was analyzed using proteomics. In Chapter 3, molecular responses of keratinocytes to extracts from THS impregnated fabric were determined.
Results: In Chapter #1, urinary biomarkers of exposure, effect, and potential harm were elevated in EC users and cigarette smokers; increased EC usage was correlated with elevated metal concentrations, which correlated with oxidative DNA damage. In Chapter #2, THS-exposure significantly elevated urinary 8-OHdG, 8-isoprostane, and protein carbonyls and activated pathways associated with inflammation, oxidative stress, and skin disease initiation. In Chapter #3, THS in keratinocytes caused proinflammation, and oxidative stress, mitochondrial damage, and elevated keratin 5 levels.
Conclusion: Cigarette smoking and EC vaping elevated DNA damage by oxidization which was correlated with total metal concentrations in the urine of cigarette smokers and EC vapers, a change which may lead to disease. Dermal THS exposure significantly increased oxidative damage to DNA, lipids, and proteins in humans. Inflammation was elevated at 3 hours and persisted for 22 hours, which could in the long-term lead to disease. Keratinocytes exposed to THS extracts had elevated molecular risk factors for developing inflammatory skin diseases, including cancer. THS-induced responses in keratinocytes were similar to those in cigarette smokers, implicating THS as an environmental hazard that should be monitored.