# Oxidant Exposure and Related Harm from Tobacco Smoke

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $448,326

## Abstract

Abstract
Toxicity and negative health effects of tobacco smoking results from the inhalation of a complex mixture of over
7000 chemicals including many toxicants and carcinogens included on the FDA list of Harmful and Potentially
Harmful Constituents (HPHCs). Oxidants are a major class of toxicant abundant in tobacco smoke and are
thought to play a critical role in the development of tobacco related diseases including COPD, CVD and cancer
through the generation of oxidative stress/damage and inflammation. However, the specific oxidants most
responsible remain unclear. While several oxidants are included on the HPHC list (eg. carbonyls), one of the
most reactive, damaging and abundant classes, free radicals, are not represented. Recently we found that
delivery of radicals varied greatly (>12-fold) across cigarette brands, was substantially impacted by product
design (e.g. tobacco variety) and smoking behaviors and was high in other popular combustible products
including little filtered cigars. Radical delivery was also highly correlated with other oxidants including carbonyls
(eg. acrolein). Based upon these findings, we propose that tobacco-derived oxidants, including free radicals,
represent an important target for developing regulatory strategies aimed at reducing the harm from
combustible tobacco use. This approach is strongly supported by our preliminary findings that levels of
oxidative stress biomarkers are significantly reduced in smokers who switch from high to low oxidant
cigarettes. The objectives of this project are to identify specific oxidants responsible for the generation of
tobacco related harm and determine the impact of oxidant reduction on tobacco-related toxicity endpoints. To
this end, we propose 3 specific aims. In Aim 1, we will determine the levels and identity of free radicals and
other oxidants delivered by different combustible tobacco products/brands using advanced electron
paramagnetic resonance (EPR) spectroscopy and liquid chromatography-tandem mass spectrometry (LC-
MS/MS) methodologies. In Aim 2 we conduct exposure studies in a relevant mouse model to determine the
impact of tobacco smoke oxidants on lung damage and inflammation; comparing effects of high vs. low oxidant
brands and tobacco varieties. In Aim 3, we will conduct mouse exposure studies to determine the impact of
charcoal filtration of cigarette smoke on oxidant-induced lung damage in the mouse. Overall, these studies will
significantly contribute to the field of tobacco regulatory science by focusing on the toxicological importance of
oxidant exposure. These data will be of particular value to the FDA for the development of regulatory policies
aimed at reducing harm imposed by tobacco usage.

## Key facts

- **NIH application ID:** 10191024
- **Project number:** 5R01HL147344-03
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Zachary T Bitzer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $448,326
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10191024

## Citation

> US National Institutes of Health, RePORTER application 10191024, Oxidant Exposure and Related Harm from Tobacco Smoke (5R01HL147344-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10191024. Licensed CC0.

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