E-cigarettes Increase the Risk of Adenoma Formation in Murine Colorectal Cancer Model.

Details

• Alternative Title:
  Archives of Toxicology, 2025, v. 99, no. 3: E-cigarettes Increase the Risk of Adenoma Formation in Murine Colorectal Cancer Model.
• Journal Article:
  Archives of Toxicology
• Personal Author:
  Sayed, Ibrahim M. ; Chakraborty, Anirban ; Inouye, Kaili ; Dugan, Leanne ; Tocci, Stefania ; Advani, Ira ; Park, Kenneth ; Gaboyan, Samvel ; Kasaraneni, Nikita ; Ma, Benjamin ; Hazra, Tapas K. ; Das, Soumita ; Crotty Alexander, Laura E.
• Description:
  E-cigarettes (E.cigs) cause inflammation and damage to human organs, including the lungs and heart. In the gut, E.cig vaping promotes inflammation and gut leakiness. Further, E.cig vaping increases tumorigenesis in oral and lung epithelial cells by inducing mutations and suppressing host DNA repair enzymes. It is well known that cigarette (cig) smoking increases the risk of colorectal cancer (CRC). To date, it is unknown whether E.cig vaping impacts CRC development. A mouse model of human familial adenomatous polyposis (CPC-APC) was utilized wherein a mutation in the adenomatous polyposis coli (APC) gene, CDX2-Cre-APC
  
  , leads to the development of colon adenomas within 11-16 weeks. Mice were exposed to air (controls), E.cig vaping, cig, or both (dual exposure). After 4 weeks of 2 h exposures per day (1 h of each for dual exposures), the colon was collected and assessed for polyp number and pathology scores by microscopy. Expression of inflammatory cytokines and cancer stem cell markers were quantified. DNA damage such as double-strand DNA breaks was evaluated by immunofluorescence, western blot, and gene-specific long amplicon qPCR. DNA repair enzyme levels (NEIL-2, NEIL-1, NTH1, and OGG1) were quantified by western blot. Proliferation markers were assessed by RT-qPCR and ELISA. CPC-APC mice exposed to E.cig, cig, and dual exposure developed a higher number of polyps compared to controls. Inflammatory proteins, DNA damage, and cancer stemness markers were higher in E-cig, cig, and dual-exposed mice as well. DNA damage was found to be associated with the suppression of DNA glycosylases, particularly with NEIL-2 and NTH1. E.cig and dual exposure both stimulated cancer cell stem markers (CD44, Lgr-5, DCLK1, and Ki67). The effect of E.cigs on polyp formation and CRC development was less than that of cigs, while dual exposure was more tumorigenic than either of the inhalants alone. E.cig vaping promotes CRC by stimulating inflammatory pathways, mediating DNA damage, and upregulating transcription of cancer stem cell markers. Critically, combining E.cig vaping with cig smoking leads to higher levels of tumorigenesis. Thus, while the chemical composition of these two inhalants, E.cigs and cigs, is highly disparate, they both drive the development of cancer and when combined, a highly common pattern of use, they can have additive or synergistic effects.
• Content Notes:
  Author manuscript
• Subjects:
  • Animals
  • Electronic Nicotine Delivery Systems
  • Colorectal Neoplasms
  • Disease Models, Animal
  • Mice
  • Adenoma
  • Vaping
  • DNA Glycosylases
  • DNA Damage
  • Male
  More +
• Keywords:
  • E.cig
  • Colorectal cancer
  • Cigarette smoking
  • Dual use
  • CPC-APC mice
  • DNA damage
  • DNA glycosylase
  • Inflammation
  • Stemness markers
• Source:
  Archives of Toxicology, 2025, v. 99, no. 3
• DOI:
  https://doi.org/10.1007/s00204-024-03932-x
• ISSN:
  0340-5761 ; 1432-0738
• Pubmed ID:
  39786590
• Pubmed Central ID:
  PMC12860471
• Document Type:
  Text
• Funding:
  I01 BX004767/BX/BLRD VAUnited States/ ; T32SR5359/Tobacco-Related Disease Research Program/ ; R01HL147326/GF/NIH HHSUnited States/ ; 2R01 NS073976/GF/NIH HHSUnited States/ ; R01HL137052/GF/NIH HHSUnited States/ ; R01 HL137052/HL/NHLBI NIH HHSUnited States/ ; R56NS073976./GF/NIH HHSUnited States/ ; I01 BX006447/BX/BLRD VAUnited States/ ; R56 AG069689/AG/NIA NIH HHSUnited States/ ; K24HL155884/GF/NIH HHSUnited States/ ; U01 IP000965/IP/NCIRD CDC HHSUnited States/ ; R56 NS073976/NS/NINDS NIH HHSUnited States/ ; AG069689/GF/NIH HHSUnited States/ ; R01 NS073976/NS/NINDS NIH HHSUnited States/ ; DK107585/GF/NIH HHSUnited States/ ; R01 HL147326/HL/NHLBI NIH HHSUnited States/ ; R01 DK107585/DK/NIDDK NIH HHSUnited States/ ; K24 HL155884/HL/NHLBI NIH HHSUnited States/ ; T30IP0965/Tobacco-Related Disease Research Program/
• Genre:
  Journal Article
• Pages in Document:
  1223-1236 (21 pdf pages)
• Volume:
  99
• Issue:
  3
• Download URL:
  https://stacks.cdc.gov/view/cdc/261789/cdc_261789_DS1.pdf
• File Type:
  [PDF - 1.44 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:b86eb989f24105ca88f71d4ca6cdd74d2a2c51d9f399240c5bede9c6c626be804ee847c0ff24b8b611f404f52884b9bc4d0720b4b7438ce925ebba69a9c981ba