Vaping Dose, Device Type, and E-Liquid Flavor are Determinants of DNA Damage in Electronic Cigarette Users.

INTRODUCTION: Despite the widespread use of electronic cigarettes, the long-term health consequences of vaping are largely unknown. AIMS AND METHODS: We investigated the DNA-damaging effects of vaping as compared to smoking in healthy adults, including "exclusive" vapers (never smokers), cigarette smokers only, and nonusers, matched for age, gender, and race (N = 72). Following biochemical verification of vaping or smoking status, we quantified DNA damage in oral epithelial cells of our study subjects, using a long-amplicon quantitative polymerase chain reaction assay. RESULTS: We detected significantly increased levels of DNA damage in both vapers and smokers as compared to nonusers (p = .005 and p = .020, respectively). While the mean levels of DNA damage did not differ significantly between vapers and smokers (p = .522), damage levels increased dose-dependently, from light users to heavy users, in both vapers and smokers as compared to nonusers. Among vapers, pod users followed by mod users, and those who used sweet-, mint or menthol-, and fruit-flavored e-liquids, respectively, showed the highest levels of DNA damage. The nicotine content of e-liquid was not a predictor of DNA damage in vapers. CONCLUSIONS: This is the first demonstration of a dose-dependent formation of DNA damage in vapers who had never smoked cigarettes. Our data support a role for product characteristics, specifically device type and e-liquid flavor, in the induction of DNA damage in vapers. Given the popularity of pod and mod devices and the preferability of sweet-, mint or menthol-, and fruit-flavored e-liquids by both adult- and youth vapers, our findings can have significant implications for public health and tobacco products regulation. IMPLICATIONS: We demonstrate a dose-dependent formation of DNA damage in oral cells from vapers who had never smoked tobacco cigarettes as well as exclusive cigarette smokers. Device type and e-liquid flavor determine the extent of DNA damage detected in vapers. Users of pod devices followed by mod users, and those who use sweet-, mint or menthol-, and fruit-flavored e-liquids, respectively, show the highest levels of DNA damage when compared to nonusers. Given the popularity of pod and mod devices and the preferability of these same flavors of e-liquid by both adult- and youth vapers, our findings can have significant implications for public health and tobacco products regulation.

Secondhand smoke affects reproductive functions by altering the mouse testis transcriptome, and leads to select intron retention in Pde1a.

BACKGROUND: Human exposure to secondhand smoke (SHS) is known to result in adverse effects in multiple organ systems. However, the impact of SHS on the male reproductive system, particularly on the regulation of genes and molecular pathways that govern sperm production, maturation, and functions remains largely understudied. OBJECTIVE: We investigated the effects of SHS on the testis transcriptome in a validated mouse model. METHODS: Adult male mice were exposed to SHS (5 h/day, 5 days/week for 4 months) as compared to controls (clean air-exposed). RNA-seq analysis was performed on the testis of SHS-exposed mice and controls. Variant discovery and plink association analyses were also conducted to detect exposure-related transcript variants in SHS-treated mice. RESULTS: Exposure of mice to SHS resulted in the aberrant expression of 131 testicular genes. Whilst approximately two thirds of the differentially expressed genes were protein-coding, the remaining (30.5%) comprised noncoding elements, mostly lncRNAs (19.1%). Variant discovery analysis identified a homozygous frameshift variant that is statistically significantly associated with SHS exposure (P = 7.744e-06) and is generated by retention of a short intron within Pde1a, a key regulator of spermatogenesis. Notably, this SHS-associated intron variant harbors an evolutionarily conserved, premature termination codon (PTC) that disrupts the open reading frame of Pde1a, presumably leading to its degradation via nonsense-mediated decay. DISCUSSION: SHS alters the expression of genes involved in molecular pathways that are crucial for normal testis development and function. Preferential targeting of lncRNAs in the testis of SHS-exposed mice is especially significant considering their crucial role in the spatial and temporal modulation of spermatogenesis. Equally important is our discovery of a novel homozygous frameshift variant that is exclusively and significantly associated with SHS-exposure and is likely to represent a safeguard mechanism to regulate transcription of Pde1a and preserve normal testis function during harmful exposure to environmental agents.