# Electronic Cigarette-derived Oxidants and their Impact on Lung Cancer Development

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $655,675

## Abstract

Abstract
Cigarette smoke is a major source of reactive oxidants, including free radicals and aldehydes, which are playing
critical roles in the development and progression of most tobacco-caused diseases including lung cancer. With
the rapidly growing popularity of electronic cigarettes (EC), there is growing concern about potential harm
associated with their use. Using state-of-the-art high resolution analytical methods to detect and measure
oxidants, we have demonstrated that EC aerosols contain significant levels of highly reactive free radicals and
aldehydes. While these oxidants were detected in all types of EC tested, their levels varied substantially by EC
product design, flavor additives, and usage behaviors. Based on these studies and the known importance of
oxidative stress/damage and inflammation in lung carcinogenesis, our proposal focuses on the potential impact
of EC-derived free radicals and aldehydes in mechanisms involved in lung cancer development. Specifically,
we hypothesize that exposure to oxidants from EC use will lead to oxidative stress/damage and inflammation in
the lung resulting in increased susceptibility to cancer. We will utilize a translational approach to test this
hypothesis by first, in the laboratory, identifying the chemical identity and potential for harm for the major free
radicals produced by EC (Aim 1), secondly conducting controlled exposure studies in a relevant mouse model
on the impact of EC-aerosols on specific lung cancer-related endpoints and lung tumor development (Aim 2),
and thirdly, conduct secondary analyses of samples generated from an NIDA-funded EC clinical trial to examine
the impact of long-term switching from conventional cigarettes to ECs on relevant oxidative stress/damage and
inflammatory biomarkers (Aim 3). In Aim 1, we utilize advanced electron paramagnetic resonance (EPR)
spectroscopy techniques and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodologies to
identify major radical species in representative EC devices (including the NIDA developed standardized EC,
SREC). Aim 2 will consist of multiple short-term exposure studies in the A/J mouse, both in naïve animals and
those pre-exposed to cigarette smoke, and will also test the specific impact of flavorants, radicals and aldehydes
on systemic and tissue specific biomarkers of oxidative stress/damage, inflammation and lung-cancer related
pathways. Additionally, we will determine and compare the impact of EC aerosol and cigarette smoke exposure
on lung tumorigenesis in an NNK-induced A/J mouse model. In Aim 3, the impact of switching from conventional
cigarettes to EC on biomarkers of oxidative stress/damage and inflammation in healthy adult smokers will be
determined. Our research approach is innovative based upon its novel focus on EC-derived free radicals, use of
innovative methods and biomarkers, and its integrative translational design. With the completion of these studies,
we hope to provide much needed informa...

## Key facts

- **NIH application ID:** 9966565
- **Project number:** 1R01CA239030-01A1
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** JOHN P RICHIE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $655,675
- **Award type:** 1
- **Project period:** 2020-06-05 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966565

## Citation

> US National Institutes of Health, RePORTER application 9966565, Electronic Cigarette-derived Oxidants and their Impact on Lung Cancer Development (1R01CA239030-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9966565. Licensed CC0.

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