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. 2020 Nov 5;12(11):3274. doi: 10.3390/cancers12113274

Table 2.

The impact of e-cigarette liquid exposure based on cell models (in vitro study).

Type of Cells Characteristic of E-Liquid Action Reference
  • ▪

    Human middle ear epithelial cell (HMEEC) line

 E-liquids
(12 manufacturers)		 HMEEC viability reduction even without the application of nicotine.
E–liquids cytotoxicity affected by the flavoring agents.		 Song et al., 2018 (South Korea) [80]
  • ▪

    Human epithelial normal bronchial cells (Nuli1); human oral squamous cell carcinoma (UM-SCC-1); human premalignant dysplastic oral mucosalkeratinocyte cells (POE9n).

 E-cigarette vapor extracts (5) Dose–related ↑ of DNA damage, regardless of nicotine content.
Significantly ↑ ROS:
↓ TAC; ↓ expression of 8-oxoguanine DNA glycosylase (OGG1), an enzyme essential for the removal of oxidative DNA damage.		 Ganapathy et al., 2017 (USA) [62]
  • ▪

    Human keratinocytes (HaCaTs)

 E-cigarette aerosol extract (7 brands) ↓ keratinocyte antimicrobial activity.
Cytotoxic to cells (necrotic cell death).
Alerted macrophage and neutrophil antimicrobial function.		 Hwang et al., 2016 (USA) [76]
  • ▪

    Normal human oral keratinocytes (NHOKs)

 E-cigarette aerosol with different nicotine strength and flavors Induced oxidative stress: significant ↓ of intracellular glutathione (GSH) levels.
↑ cytotoxicity in oral epithelial cells.		 Ji at al., 2016 (USA) [77]
  • ▪

    Human gingival epithelial cells

 E-cigarette aerosol Altered cellular morphology.
↑ lactate dehydrogenase (LDH) activity.
↑ apoptotic cell numbers.		 Rouabhia et al., 2016 (Canada) [78]
  • ▪

    Human periodontal ligament fibroblasts (HPdLF); human gingival epithelium progenitors pooled (HGEPp); epigingival 3D epithelium

 E-cigarette aerosol ↑ levels of prostaglandin–E2
and ↑ cycloxygenase–2.
↑ oxidative/carbonyl and inflammatory responses,
↑ DNA damage, and ↓ histone deacetylase 2 (HDAC2) through RAGE–dependent mechanisms in gingival epithelium. Increased response in case of flavored e-cigarettes.		 Sundar et al., 2016 (USA) [79]
  • ▪

    Primary human oropharyngeal mucosal cells

 E-liquids with nicotine (2 fruit-flavored and 1 tobacco-flavored), and the corresponding base mixtures (free of nicotine and flavor) Cytotoxic to oropharyngeal tissue.
Significantly ↑ DNA fragmentation.		 Welz et al., 2016 (Germany) [26]
  • ▪

    Normal epithelial cells: spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT); HNSCC cell lines: from a metastatic lymph node (UMSCC10B), and from a primary laryngeal tumor (HN30)

 E-cigarette aerosol
PG:VG (70%/30%)
Flavors: “Classic Tobacco”, “Red American Tobacco”
Nicotine: 12 mg/mL		 Cytotoxic to epithelial cell lines.
↑ rates of apoptosis, ↑ rates of necrosis, independently of nicotine content.
DNA strand break–induction.		 Yu et al., 2016 (USA) [65]
  • ▪

    Primary human gingival fibroblasts

 E-liquids (Two kinds: with and without nicotine) Cytotoxic to cells.
Both nicotine-containing and nicotine-free liquids induced ↑ reactive oxygen species (ROS) production.		 Sancilio et al., 2015 (Italy) [75]
  • ▪

    Human periodontal ligament fibroblasts

 Test solutions with components from E-liquids: lime-, hazelnut- and menthol-flavored liquids, nicotine, propylene glycol, and PBS as control group Harmful effect of menthol additive on human periodontal ligament fibroblasts. Willershausen et al., 2014 (Germany) [74]

Explanation: ↑—increase, ↓—decrease.