title: A C. elegans model of electronic cigarette use: Physiological effects of e-liquids in nematodes.
abstract: BACKGROUND
  Electronic cigarettes (e-cigs) have recently become very popular particularly among the younger generation. These nicotine delivery devices are viewed as a preferable alternative to more conventional forms of tobacco use and are thought to reduce the risk of chronic obstructive pulmonary disease, the third leading cause of death worldwide. However, there is very little data available on the consequences of e-cig use, though recently nicotine-independent inflammatory responses have been reported. The genetic model organism Caenorhabditis elegans is a soil nematode whose cell biology is remarkably well conserved with mammals. Here, we used C. elegans to test the physiologic effects of e-liquids used to refill e-cigs.
  
  
  METHODS
  Larval worms were exposed from hatching onwards to low concentrations (0.2 %) of e-liquids, distilled e-liquid vapor, propylene glycol (PG), or M9 buffer as a negative control. E-liquids tested included grape, menthol, and V2 Red "classic tobacco" flavors. Nicotine (48 ppm) was tested as a second level variable. Stereotypical physiological outputs were then measured, including developmental rate, fecundity, locomotion, lifespan, and the induction of canonical stress signaling pathways.
  
  
  RESULTS
  A small but significant impairment of developmental rate and brood size was observed for PG and V2 Red treated worms compared to the negative control. Worms treated with e-liquids containing nicotine fared significantly worse than those that did not, but vaporization did not increase toxicity. Finally, both PG and V2 Red e-liquid induced an oxidative stress response in the absence of nicotine.
  
  
  CONCLUSIONS
  PG exposure is sufficient to induce an oxidative stress response in nematodes, while nicotine is not. Both PG and nicotine independently influence physiologic measures of health and viability. The e-liquid flavorings did not significantly impact outcomes and there was no evidence for vaporization altering toxicity. These data suggest that the major physiologically significant component of e-liquids besides nicotine is likely the common solvent PG. We conclude that C. elegans are an appropriate model to rapidly assess parameters that may contribute to the basic cell biological effects of e-cigs.
authors.affiliation: Department of Biotechnology Engineering, ORT Braude College, Karmiel, Israel. danielp2345@hotmail.com.|Department of Medicine and Pharmacology & Physiology, University of Rochester Medical Center, Rochester, NY, USA. danielp2345@hotmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Panitz
authors.affiliation: Department Pharmacology & Physiology, University of Rochester Medical Center, Rochester, NY, USA. harsha_swamy@urmc.rochester.edu.
authors.forename: Harsha
authors.initials: H
authors.lastname: Swamy
authors.affiliation: Department of Medicine and Pharmacology & Physiology, University of Rochester Medical Center, Rochester, NY, USA. keith_nehrke@urmc.rochester.edu.|Department Pharmacology & Physiology, University of Rochester Medical Center, Rochester, NY, USA. keith_nehrke@urmc.rochester.edu.|Department of Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, Box 675, NY, 14642, USA. keith_nehrke@urmc.rochester.edu.
authors.forename: Keith
authors.initials: K
authors.lastname: Nehrke
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D066300:Electronic Nicotine Delivery Systems / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008610:Menthol / Q000008:administration & dosage / Q000494:pharmacology; D018613:Microscopy, Confocal; D023421:Models, Animal; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D019946:Propylene Glycol / Q000008:administration & dosage / Q000494:pharmacology*; D014026:Nicotiana / Q000737:chemistry; D014835:Volatilization
chemical_list: D049452:Green Fluorescent Proteins; D008610:Menthol; D019946:Propylene Glycol; D009538:Nicotine