Biomarkers of disease can be detected in mice as early as 4 weeks after initiation of exposure to third-hand smoke levels equivalent to those found in homes of smokers

Abstract

Third-hand smoke (THS) is a newly discovered environmental health hazard that results from accumulation and aging of second-hand smoke (SHS) toxins on surfaces where smoking has occurred. Our objective was to determine whether there is a time-dependent effect of THS exposure on health. Using an in vivo exposure mouse system that mimics exposure of humans to THS, we investigated its effects on biomarkers found in serum, and in liver and brain tissues. Mice were exposed to THS for 1, 2, 4, or 6 months and brain, liver, and serum were collected. We found that THS exposure, as early as 1 month, resulted in increased circulating inflammatory cytokines, tumor necrosis factor by an order of magnitude of 2 and granulocyte macrophage colony-stimulating factor by an order of magnitude of 1.5 and in increases in the stress hormone epinephrine and the liver damage biomarker aspartate aminotransferase (AST), increased in magnitude 1.5 and 2.5 times compared with controls, respectively. THS exposure for 2 months resulted in further damage and at 4 and 6 months, many factors related to oxidative stress were altered and caused molecular damage. We also found that the mice became hyperglycemic and hyperinsulinimic suggesting that insulin resistance (IR) may be a significant consequence of long-term exposure to THS. In conclusion, time-dependent THS exposure has a significant effect on health as early as 1 month after initiation of exposure and these alterations progressively worsen with time. Our studies are important because virtually nothing is known about the effects of increased THS exposure time, they can serve to educate the public on the dangers of THS, and the biomarkers we identified can be used in the clinic, once verified in exposed humans.

Biological markers of harm can be detected in mice exposed for two months to low doses of Third Hand Smoke under conditions that mimic human exposure

“…In our previous time-dependent study, the brain takes much longer (4 months) for THS exposure with the 40 cigarette-smoking regimen to result in the accumulation of H 2 O 2 (Adhami et al, 2017). We speculate that the blood-brain barrier is most likely the reason why the brain is more "protected" from THS exposure and molecular damage takes longer to occur.…”

“…For all of the studies shown here, we investigated levels of molecules that had shown to be altered in our previous studies of the timedependent effect of THS exposure (Adhami et al, 2017). We chose to determine whether those same molecules were altered in a dose-dependent manner in the serum, and liver and brain tissues of different cohorts of mice exposed for 2 month to doses of THS generated by the 10, 20 and 40 cigarette-smoking regimen and tested these mice against 13 BMH (Table 1).…”

“…Children and infants are at most risk for being exposed to THS toxins because they are in closer contact with household surfaces; they frequently put their hands in the mouths and also their surface to volume ratio is large allowing for the absorption of these toxins through the skin in a much more effective way (Ferrante et al, 2013). We have previously determined the minimum amount of time required to cause physiological changes in mice when they were exposed to THS under conditions that mimic human exposure (Adhami et al, 2017). Our findings suggest that specific Biological Markers of Harm (BMH) can potentially be used to determine how long children have been exposed to THS toxins and the extent of cellular and molecular damage that could lead to disease.…”

“…In our study to investigate the dose effects to THS exposure, we narrowed the scope of the work to focus on the BMH that were altered by 2-month of exposure. Therefore, the specific BMH that we chose to study are those that are altered at 2 months of THS exposure to the 40 cigarette-smoking regimen (Adhami et al, 2017). We asked the question: What is the minimum dose of exposure required for these toxins to cause harm?…”

Levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in raw wastewater as an innovative perspective for investigating population-wide exposure to third-hand smoke

“…dusts) and dermal uptake from contact with contaminated surfaces and clothes/textiles, as well as ingestion from the hands or food that are exposed to tobacco smoke 7 . Negative health impacts of THS exposure on rodents have been recently revealed 8,14 ; however, further studies are required to assess health risks for humans.…”