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

Journal Article · · Environment International
 [1];  [2];  [3];  [4];  [5];  [5];  [5];  [6];  [7];  [8];  [6];  [6];  [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
+ Show Author Affiliations
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, Journal Name: Environment International Vol. 174; ISSN 0160-4120
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

60 APPLIED LIFE SCIENCES
Collaborative Cross (CC) mice
genetic susceptibility
pan-tumor incidence
thirdhand smoke (THS)
tumor burden
tumor-free survival
tumorigenesis