TY - JOUR AU - Bo Hang AU - Yunshan Wang AU - Yurong Huang AU - Pin Wang AU - Sasha A Langley AU - Lei Bi AU - Altaf H Sarker AU - Suzaynn F Schick AU - Christopher Havel AU - Peyton Jacob III AU - Neal L Benowitz AU - Hugo Destaillats AU - Xiaochen Tang AU - Yankai Xia AU - Kuang-Yu Jen AU - Lara A Gundel AU - Jian-Hua Mao AU - Antoine M Snijders AB -

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.

BT - Clinical Science DA - 02/2018 DO - 10.1042/CS20171521 IS - 4 LA - eng N2 -

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.

PY - 2018 SP - 475 EP - 488 T2 - Clinical Science TI - Short-term early exposure to thirdhand cigarette smoke increases lung cancer incidence in mice VL - 132 ER -