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Title: Thirdhand tobacco smoke exposure increases the genetic background-dependent risk of pan-tumor development in Collaborative Cross mice

Journal Article · · Environment International
 [1];  [2]; ORCiD logo [3];  [4];  [5];  [5];  [5];  [6];  [7];  [8]; ORCiD logo [6];  [6]; ORCiD logo [6];  [6];  [6]
  1. Wuhan Univ. (China). Hubei Key Laboratory of Tumor Biological Behaviors
  2. Nanjing Univ. of Chinese Medicine (China)
  3. Nanjing Univ. (China)
  4. Wuhan Univ. (China)
  5. Univ. of California, San Francisco, CA (United States)
  6. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
  7. Rice Univ., Houston, TX (United States)
  8. Nanjing Medical Univ. (China). State Key Laboratory of Reproductive Medicine

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
2229053
Journal Information:
Environment International, Vol. 174; ISSN 0160-4120
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

References (44)

Giving the Genes a Shuffle: Using Natural Variation to Understand Host Genetic Contributions to Viral Infections journal October 2018
Genetic background influences the effect of thirdhand smoke exposure on anxiety and memory in Collaborative Cross mice journal June 2021
Gut microbiome partially mediates and coordinates the effects of genetics on anxiety-like behavior in Collaborative Cross mice journal January 2021
Dermal thirdhand smoke exposure induces oxidative damage, initiates skin inflammatory markers, and adversely alters the human plasma proteome journal October 2022
Formation of carcinogens indoors by surface-mediated reactions of nicotine with nitrous acid, leading to potential thirdhand smoke hazards journal February 2010
Effect of cigarette smoking on major histological types of lung cancer: a meta-analysis journal March 2001
Secondary organic aerosol formation from ozone-initiated reactions with nicotine and secondhand tobacco smoke journal November 2010
Chemical changes in thirdhand smoke associated with remediation using an ozone generator journal July 2021
Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice journal November 2015
Thirdhand smoke contamination in hospital settings: assessing exposure risk for vulnerable paediatric patients: Table 1 journal December 2015
Thirdhand Cigarette Smoke: Factors Affecting Exposure and Remediation journal October 2014
Thirdhand Smoke: New Evidence, Challenges, and Future Directions journal December 2016
Tobacco Alkaloids and Tobacco-Specific Nitrosamines in Dust from Homes of Smokeless Tobacco Users, Active Smokers, and Nontobacco Users journal April 2015
Early exposure to thirdhand cigarette smoke affects body mass and the development of immunity in mice journal February 2017
Thirdhand smoke exposure causes replication stress and impaired transcription in human lung cells journal April 2020
From the Cover: Thirdhand Cigarette Smoke Causes Stress-Induced Mitochondrial Hyperfusion and Alters the Transcriptional Profile of Stem Cells journal June 2016
Identification and determination of the volatile organics of third-hand smoke from different cigarettes and clothing fabrics journal February 2022
Thirdhand Tobacco Smoke: Emerging Evidence and Arguments for a Multidisciplinary Research Agenda journal September 2011
Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing journal June 2016
Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome journal November 2016
Thirdhand smoke causes DNA damage in human cells journal March 2013
Thirdhand cigarette smoke in an experimental chamber: evidence of surface deposition of nicotine, nitrosamines and polycyclic aromatic hydrocarbons and de novo formation of NNK journal May 2013
Genetic and metabolic links between the murine microbiome and memory journal April 2020
Effect of Ozone on Nicotine Desorption from Model Surfaces:  Evidence for Heterogeneous Chemistry journal March 2006
Genetic Susceptibility to Thirdhand-Smoke-Induced Lung Cancer Development journal June 2018
Short-term early exposure to thirdhand cigarette smoke increases lung cancer incidence in mice journal February 2018
Formation and Repair of Tobacco Carcinogen-Derived Bulky DNA Adducts journal January 2010
Differential associations of hand nicotine and urinary cotinine with children's exposure to tobacco smoke and clinical outcomes journal November 2021
Persistent tobacco smoke residue in multiunit housing: Legacy of permissive indoor smoking policies and challenges in the implementation of smoking bans journal June 2020
Light-Stress Influences the Composition of the Murine Gut Microbiome, Memory Function, and Plasma Metabolome journal October 2019
Cigarette Smoke Toxins Deposited on Surfaces: Implications for Human Health journal January 2014
Urine 4-(methylnitrosamino)-1-(3) pyridyl-1-butanol and cotinine in Alaska native postpartum women and neonates comparing smokers and smokeless tobacco users journal January 2018
Diverse tumour susceptibility in Collaborative Cross mice: identification of a new mouse model for human gastric tumourigenesis journal March 2019
Characterization of adductomic totality of NNK, (R)-NNAL and (S)-NNAL in A/J mice, and their correlations with distinct lung carcinogenicity journal December 2021
When smokers move out and non-smokers move in: residential thirdhand smoke pollution and exposure journal October 2010
Thirdhand Exposures to Tobacco-Specific Nitrosamines through Inhalation, Dust Ingestion, Dermal Uptake, and Epidermal Chemistry journal July 2022
Inhalable Constituents of Thirdhand Tobacco Smoke: Chemical Characterization and Health Impact Considerations journal October 2014
The Collaborative Cross, a community resource for the genetic analysis of complex traits journal January 2004
From in utero and childhood exposure to parental smoking to childhood cancer: a possible link and the need for action journal April 1999
Rapid single-dose model for lung tumor induction in A/J mice by 4-(methylnitrosainino)-1-(3-pyridyl)-1-butanone and the effect of diet journal January 1989
A/J Mouse As A Model For Lung Tumorigenesis Caused By Tobacco Smoke: Strengths And Weaknesses journal January 2004
Cytotoxicity of Thirdhand Smoke and Identification of Acrolein as a Volatile Thirdhand Smoke Chemical That Inhibits Cell Proliferation journal December 2015
The Genome Architecture of the Collaborative Cross Mouse Genetic Reference Population journal January 2012
Prenatal Exposure to Parents' Smoking and Childhood Cancer journal January 1991