Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage

Vengatesh Ganapathy, Jimmy Manyanga, Lacy Brame, Dehra McGuire, Balaji Sadhasivam, Evan Floyd, David A. Rubenstein, Ilangovan Ramachandran, Theodore Wagener, Lurdes Queimado

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Electronic cigarette (EC) aerosols contain unique compounds in addition to toxicants and carcinogens traditionally found in tobacco smoke. Studies are warranted to understand the public health risks of ECs. Objective: The aim of this study was to determine the genotoxicity and the mechanisms induced by EC aerosol extracts on human oral and lung epithelial cells. Methods: Cells were exposed to EC aerosol or mainstream smoke extracts and DNA damage was measured using the primer anchored DNA damage detection assay (q-PADDA) and 8-oxo-dG ELISA assay. Cell viability, reactive oxygen species (ROS) and total antioxidant capacity (TAC) were measured using standard methods. mRNA and protein expression were evaluated by RT-PCR and western blot, respectively. Results: EC aerosol extracts induced DNA damage in a dose-dependent manner, but independently of nicotine concentration. Overall, EC aerosol extracts induced significantly less DNA damage than mainstream smoke extracts, as measured by q-PADDA. However, the levels of oxidative DNA damage, as indicated by the presence of 8-oxo-dG, a highly mutagenic DNA lesion, were similar or slightly higher after exposure to EC aerosol compared to mainstream smoke extracts. Mechanistically, while exposure to EC extracts significantly increased ROS, it decreased TAC as well as the expression of 8-oxoguanine DNA glycosylase (OGG1), an enzyme essential for the removal of oxidative DNA damage. Conclusions: Exposure to EC aerosol extracts suppressed the cellular antioxidant defenses and led to significant DNA damage. These findings emphasize the urgent need to investigate the potential long-term cancer risk of exposure to EC aerosol for vapers and the general public.

Original languageEnglish
Article numbere0177780
JournalPLoS ONE
Volume12
Issue number5
DOIs
StatePublished - 1 May 2017

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cigarettes
aerosols
Aerosols
Tobacco Products
DNA damage
DNA Damage
electronics
Antioxidants
antioxidant activity
DNA
extracts
smoke
Smoke
reactive oxygen species
Assays
Reactive Oxygen Species
Public risks
DNA Glycosylases
glycosylases
antioxidants

Cite this

Ganapathy, V., Manyanga, J., Brame, L., McGuire, D., Sadhasivam, B., Floyd, E., ... Queimado, L. (2017). Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage. PLoS ONE, 12(5), [e0177780]. https://doi.org/10.1371/journal.pone.0177780
Ganapathy, Vengatesh ; Manyanga, Jimmy ; Brame, Lacy ; McGuire, Dehra ; Sadhasivam, Balaji ; Floyd, Evan ; Rubenstein, David A. ; Ramachandran, Ilangovan ; Wagener, Theodore ; Queimado, Lurdes. / Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage. In: PLoS ONE. 2017 ; Vol. 12, No. 5.
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abstract = "Background: Electronic cigarette (EC) aerosols contain unique compounds in addition to toxicants and carcinogens traditionally found in tobacco smoke. Studies are warranted to understand the public health risks of ECs. Objective: The aim of this study was to determine the genotoxicity and the mechanisms induced by EC aerosol extracts on human oral and lung epithelial cells. Methods: Cells were exposed to EC aerosol or mainstream smoke extracts and DNA damage was measured using the primer anchored DNA damage detection assay (q-PADDA) and 8-oxo-dG ELISA assay. Cell viability, reactive oxygen species (ROS) and total antioxidant capacity (TAC) were measured using standard methods. mRNA and protein expression were evaluated by RT-PCR and western blot, respectively. Results: EC aerosol extracts induced DNA damage in a dose-dependent manner, but independently of nicotine concentration. Overall, EC aerosol extracts induced significantly less DNA damage than mainstream smoke extracts, as measured by q-PADDA. However, the levels of oxidative DNA damage, as indicated by the presence of 8-oxo-dG, a highly mutagenic DNA lesion, were similar or slightly higher after exposure to EC aerosol compared to mainstream smoke extracts. Mechanistically, while exposure to EC extracts significantly increased ROS, it decreased TAC as well as the expression of 8-oxoguanine DNA glycosylase (OGG1), an enzyme essential for the removal of oxidative DNA damage. Conclusions: Exposure to EC aerosol extracts suppressed the cellular antioxidant defenses and led to significant DNA damage. These findings emphasize the urgent need to investigate the potential long-term cancer risk of exposure to EC aerosol for vapers and the general public.",
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Ganapathy, V, Manyanga, J, Brame, L, McGuire, D, Sadhasivam, B, Floyd, E, Rubenstein, DA, Ramachandran, I, Wagener, T & Queimado, L 2017, 'Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage', PLoS ONE, vol. 12, no. 5, e0177780. https://doi.org/10.1371/journal.pone.0177780

Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage. / Ganapathy, Vengatesh; Manyanga, Jimmy; Brame, Lacy; McGuire, Dehra; Sadhasivam, Balaji; Floyd, Evan; Rubenstein, David A.; Ramachandran, Ilangovan; Wagener, Theodore; Queimado, Lurdes.

In: PLoS ONE, Vol. 12, No. 5, e0177780, 01.05.2017.

Research output: Contribution to journalArticle

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T1 - Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage

AU - Ganapathy, Vengatesh

AU - Manyanga, Jimmy

AU - Brame, Lacy

AU - McGuire, Dehra

AU - Sadhasivam, Balaji

AU - Floyd, Evan

AU - Rubenstein, David A.

AU - Ramachandran, Ilangovan

AU - Wagener, Theodore

AU - Queimado, Lurdes

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Background: Electronic cigarette (EC) aerosols contain unique compounds in addition to toxicants and carcinogens traditionally found in tobacco smoke. Studies are warranted to understand the public health risks of ECs. Objective: The aim of this study was to determine the genotoxicity and the mechanisms induced by EC aerosol extracts on human oral and lung epithelial cells. Methods: Cells were exposed to EC aerosol or mainstream smoke extracts and DNA damage was measured using the primer anchored DNA damage detection assay (q-PADDA) and 8-oxo-dG ELISA assay. Cell viability, reactive oxygen species (ROS) and total antioxidant capacity (TAC) were measured using standard methods. mRNA and protein expression were evaluated by RT-PCR and western blot, respectively. Results: EC aerosol extracts induced DNA damage in a dose-dependent manner, but independently of nicotine concentration. Overall, EC aerosol extracts induced significantly less DNA damage than mainstream smoke extracts, as measured by q-PADDA. However, the levels of oxidative DNA damage, as indicated by the presence of 8-oxo-dG, a highly mutagenic DNA lesion, were similar or slightly higher after exposure to EC aerosol compared to mainstream smoke extracts. Mechanistically, while exposure to EC extracts significantly increased ROS, it decreased TAC as well as the expression of 8-oxoguanine DNA glycosylase (OGG1), an enzyme essential for the removal of oxidative DNA damage. Conclusions: Exposure to EC aerosol extracts suppressed the cellular antioxidant defenses and led to significant DNA damage. These findings emphasize the urgent need to investigate the potential long-term cancer risk of exposure to EC aerosol for vapers and the general public.

AB - Background: Electronic cigarette (EC) aerosols contain unique compounds in addition to toxicants and carcinogens traditionally found in tobacco smoke. Studies are warranted to understand the public health risks of ECs. Objective: The aim of this study was to determine the genotoxicity and the mechanisms induced by EC aerosol extracts on human oral and lung epithelial cells. Methods: Cells were exposed to EC aerosol or mainstream smoke extracts and DNA damage was measured using the primer anchored DNA damage detection assay (q-PADDA) and 8-oxo-dG ELISA assay. Cell viability, reactive oxygen species (ROS) and total antioxidant capacity (TAC) were measured using standard methods. mRNA and protein expression were evaluated by RT-PCR and western blot, respectively. Results: EC aerosol extracts induced DNA damage in a dose-dependent manner, but independently of nicotine concentration. Overall, EC aerosol extracts induced significantly less DNA damage than mainstream smoke extracts, as measured by q-PADDA. However, the levels of oxidative DNA damage, as indicated by the presence of 8-oxo-dG, a highly mutagenic DNA lesion, were similar or slightly higher after exposure to EC aerosol compared to mainstream smoke extracts. Mechanistically, while exposure to EC extracts significantly increased ROS, it decreased TAC as well as the expression of 8-oxoguanine DNA glycosylase (OGG1), an enzyme essential for the removal of oxidative DNA damage. Conclusions: Exposure to EC aerosol extracts suppressed the cellular antioxidant defenses and led to significant DNA damage. These findings emphasize the urgent need to investigate the potential long-term cancer risk of exposure to EC aerosol for vapers and the general public.

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