Journal
CLINICAL SCIENCE
Volume 132, Issue 4, Pages 475-488Publisher
PORTLAND PRESS LTD
DOI: 10.1042/CS20171521
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Funding
- University of California Tobacco-Related Disease Research Program (TRDRP) [24RT-0038, 23PT-0013]
- Lawrence Berkeley National Laboratory Directed Research and Development (LDRD) program [DE AC02-05CH11231]
- National Institute on Drug Abuse [P30 DA012393]
- National Center for Research Resources [S10 RR026437]
- National Science Foundation of China [81402193]
- Postdoctoral innovation project of Shandong Province
- Postdoctoral Science Foundation of China
- China Postdoctoral International Exchange Program
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Exposure to thirdhand smoke (THS) is a recently described health concern that arises in many indoor environments. However, the carcinogenic potential of THS, a critical consideration in risk assessment, remains untested. Here we investigated the effects of short-term early exposure to THS on lung carcinogenesis in A/J mice. Forty weeks after THS exposure from 4 to 7 weeks of age, the mice had increased incidence of lung adenocarcinoma, tumor size and, multiplicity, compared with controls. In vitro studies using cultured human lung cancer cells showed that THS exposure induced DNA double-strand breaks and increased cell proliferation and colony formation. RNA sequencing analysis revealed that THS exposure induced endoplasmic reticulum stress and activated p53 signaling. Activation of the p53 pathway was confirmed by an increase in its targets p21 and BAX. These data indicate that early exposure to THS is associated with increased lung cancer risk.
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