Thirdhand tobacco smoke exposure increases the genetic background-dependent risk of pan-tumor development in Collaborative Cross mice. (April 2023)

• Record Type: Journal Article
• Authors: Yang, Hui; Wang, Xinzhi; Wang, Pin; He, Li; Schick, Suzyann F.; Jacob, Peyton; Benowitz, Neal; Gundel, Lara A.; Zhu, Chi; Xia, Yankai; Inman, Jamie L.; Chang, Hang; Snijders, Antoine M.; Mao, Jian-Hua; Hang, Bo
• Is Part Of: Environment international. Volume 174(2023)
• Publication Date: 2023-04
• Subjects: Thirdhand smoke (THS) -- Collaborative Cross (CC) mice -- Genetic susceptibility -- Tumorigenesis -- Pan-tumor incidence -- Tumor burden -- Tumor-free survival; THS thirdhand smoke -- SHS secondhand smoke -- PAH polycyclic aromatic hydrocarbon -- TSNA Tobacco-specific nitrosamine -- CC Collaborative Cross -- TFS Tumor-free survival -- TLY Thymic lymphoma -- SLY Splenic lymphoma -- ALY Abdominal lymphoma -- SCLC small cell lung carcinoma -- HCC Hepatic cell carcinoma -- SNP Single Nucleotide Polymorphism; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2023.107876
• Languages: English
• ISSNs: 0160-4120

Abstract

Highlights: THS exposure significantly increased pan-tumor incidence in CC mice. THS exposure significantly reduced pan-tumor-free survival in CC mice. Tumor susceptibility after THS exposure varied significantly across different CC strains. Genetic background plays an important role in THS exposure-induced mouse tumorigenesis. Abstract: Increasing evidence has shown that thirdhand smoke (THS) exposure is likely to induce adverse health effects. An important knowledge gap remains in our understanding of THS exposure related to cancer risk in the human population. Population-based animal models are useful and powerful in investigating the interplay between host genetics and THS exposure on cancer risk. Here, we used the Collaborative Cross (CC) mouse population-based model system, which recapitulates the genetic and phenotypic diversity observed in the human population, to assess cancer risk after a short period of exposure, between 4 and 9 weeks of age. Eight CC strains (CC001, CC019, CC026, CC036, CC037, CC041, CC042 and CC051) were included in our study. We quantified pan-tumor incidence, tumor burden per mouse, organ tumor spectrum and tumor-free survival until 18 months of age. At the population level, we observed a significantly increased pan-tumor incidence and tumor burden per mouse in THS-treated mice as compared to the control ( p = 3.04E-06). Lung and liver tissues exhibited the largest risk of undergoing tumorigenesis after THS exposure. Tumor-free survival was significantly reduced in THS-treated mice compared to control ( p = 0.044). At the individual strain level, we observed a large variation in tumor incidence across the 8 CC strains. CC036 and CC041 exhibited a significant increase in pan-tumor incidence ( p = 0.0084 and p = 0.000066, respectively) after THS exposure compared to control. We conclude that early-life THS exposure increases tumor development in CC mice and that host genetic background plays an important role in individual susceptibility to THS-induced tumorigenesis. Genetic background is an important factor that should be taken into account when determining human cancer risk of THS exposure.