# Project 3 - Ethnic/racial Differences in Metabolism and DNA Adduct Formation by 1,3-Butadiene

> **NIH NIH P01** · UNIVERSITY OF MINNESOTA · 2020 · $219,620

## Abstract

ABSTRACT 
Butadiene is an important tobacco smoke carcinogen likely to be involved in the induction of lung tumors 
in smokers. Butadiene is classified as a known human carcinogen based on epidemiological evidence 
indicating increased cancer incidence in occupationally exposed workers and in inhalation studies in 
laboratory animals. The recognized critical step in butadiene-mediated carcinogenesis is the chemical 
modification of DNA by the epoxide metabolites of butadiene to form covalent adducts. Previous studies 
have shown that genetic variations in metabolism and repair genes can mediate the sensitivity to 
butadiene-induced mutations and cancer. Because of the requirement for metabolic activation of 
butadiene, enzymes that are involved in the formation and detoxification of butadiene epoxides largely 
determine the individual sensitivity to butadiene-mediated mutagenesis and carcinogenesis. Many 
prominent polymorphisms in genes coding for butadiene metabolizing enzymes have been identified. 
Because their frequency differs between ethnic/racial groups, these genetic changes may contribute to 
the observed inter-ethnic/inter-racial differences in the incidence of lung cancer. In the previous funding 
period, we observed significant ethnic differences in the excretion of urinary butadiene-mercapturic 
acids by White, African American, Japanese American, and Native Hawaiian smokers. These results 
indicate that these ethnic groups metabolize butadiene differently due to genetic variations in 
biotransformation genes such as glutathione-S-transferase 1 (GSTT1). 
We now hypothesize that due to ethnic variations in butadiene metabolism, human populations of 
different ethnicity/race form different numbers of butadiene-DNA adducts, which contributes to ethnic 
disparities in cancer risk following exposure to butadiene in tobacco smoke. The objective of this 
application is to investigate inter-individual and inter-ethnic/racial differences in formation of butadiene- 
induced DNA adducts in smokers, to establish their role in lung cancer risk, and to link inter-individual 
differences in response to butadiene to specific polymorphisms of carcinogen metabolism and DNA 
repair genes. Our approach is innovative because we will, for the first time, examine butadiene-DNA 
adduct formation in a large multi-ethnic cohort of smokers, evaluate the association between butadiene 
exposure and lung cancer, and evaluate the effects of specific genetic polymorphisms on butadiene 
metabolism, DNA adduct formation, toxicity, and mutations in human HapMap cell cultures. 
Expected outcomes: Although smoking is a recognized risk factor for lung cancer, one out of five 
Americans continue to smoke. About 11-24 % of smokers will develop lung tumors over the lifetime, with 
a greater cancer incidence in African American and Native Hawaiian cigarette smokers as compared with 
European Americans, Japanese Americans, and Latinos. Our studies will help provide insight i...

## Key facts

- **NIH application ID:** 9994213
- **Project number:** 5P01CA138338-10
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** NATALIA Y TRETYAKOVA
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $219,620
- **Award type:** 5
- **Project period:** — → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994213

## Citation

> US National Institutes of Health, RePORTER application 9994213, Project 3 - Ethnic/racial Differences in Metabolism and DNA Adduct Formation by 1,3-Butadiene (5P01CA138338-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9994213. Licensed CC0.

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