Oncotarget 1

www.impactjournals.com/oncotarget

www.impactjournals.com/oncotarget/ Oncotarget, Advance Publications 2016

E-cigarettes and avorings induce inammatory and pro-

senescence responses in oral epithelial cells and periodontal

broblasts

Isaac K. Sundar 1 , Fawad Javed 2 , Georgios E. Romanos 3 , Irfan Rahman 1

1 Department of Environmental Medicine, University of Rochester Medical Center , Rochester , NY

2 Department of General Dentistry , Eastman Institute for Oral Health University of Rochester , Rochester, NY

3 Department of Periodontology , School of Dental Medicine, Stony Brook University, Stony Brook, NY

Correspondence to: Irfan Rahman, email: irfan_rahman@urmc.rochester .edu

Keywords: e-cigarettes, e-juices, RAGE, COX 2 , PGE 2

Received: August 02, 2016 Accepted: October 14, 2016 Published: October 24, 2016

ABSTRACT

Electronic-cigarettes (e-cigs) represent a signicant and increasing proportion

of tobacco product consumption, which may pose an oral health concern. Oxidative/

carbonyl stress via protein carbonylation is an important factor in causing inammation

and DNA damage. This results in stress-induced premature senescence (a state of

irreversible growth arrest which re-enforces chronic inammation) in gingival

epithelium, which may contribute to the pathogenesis of oral diseases. We show that

e-cigs with avorings cause increased oxidative/carbonyl stress and inammatory

cytokine release in human periodontal ligament broblasts, Human Gingival Epithelium

Progenitors pooled (HGEPp), and epigingival 3D epithelium. We further show increased

levels of prostaglandin-E2 and cycloxygenase-2 are associated with upregulation of

the receptor for advanced glycation end products (RAGE) by e-cig exposure-mediated

carbonyl stress in gingival epithelium/tissue. Further, e-cigs cause increased oxidative/

carbonyl and inammatory responses, and DNA damage along with histone deacetylase

2 (HDAC2) reduction via RAGE-dependent mechanisms in gingival epithelium. A greater

response is elicited by avored e-cigs. Increased oxidative stress, pro-inammatory

and pro-senescence responses (DNA damage and HDAC2 reduction) can result

in dysregulated repair due to proinammatory and pro-senescence responses in

periodontal cells. These data highlight the pathologic role of e-cig aerosol and its

avoring to cells and tissues of the oral cavity in compromised oral health.

INTRODUCTION

The use of electronic-cigarettes (e-cigs) is increasing

in the United States, which may pose oral health concerns

[1]. E-cigs are battery operated devices, which consist

of a metal heating element in a stainless steel shell, a

cartridge, an atomizer and a battery. The heating element

vaporizes a solution containing a mixture of chemicals

including nicotine and other additives/humectants, such as

base/carrying agents propylene glycol, glycerin/glycerol,

and avoring agents including fruit and candy avors.

Apart from inhaled nicotine, variable levels of aldehydes

and carbonyls are detected in e-cig aerosols during

vaporizations [2, 3]. Aldehyde causes carbonyl/oxidative

stress, DNA adducts/damage, as well as stress-induced

cellular senescence (a state of irreversible growth arrest

which re-enforces chronic inammation) [4, 5] leading to

oral health problems [6–8].

Periodontal disease is characterized by chronic

inammation of the supporting tissues of the teeth.

Periodontal ligament and gingival broblasts as well as

epithelial cells are the most abundant structural cells in

periodontal tissue. Upon stimulation or stress, these cells

are able to incite and maintain inammatory responses

[9]. There is an association between smoking and tooth

loss, periodontal attachment level, deeper periodontal

pockets, and more extensive alveolar bone loss along with

the destruction of connective tissue and matrix, leading