# DNA Cross-Linking By Diepoxybutane

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $309,748

## Abstract

Abstract
1,3-butadiene (butadiene) is a known human carcinogen produced industrially and also found in
automobile exhaust, cigarette smoke, and forest fires. Epoxide metabolites of butadiene, i.e.
1,2,3,4-diepoxybutane (DEB), 3,4-epoxy-1-butene (EB), and 3,4-epoxy-1,2-butanediol (EB-diol),
are thought to be the ultimate genotoxic species of BD. These epoxides preferentially modify the
N7-guanine position in DNA to give rise to N7- (2-hydroxy-3,4-epoxybutene-1-yl)-guanine (EB-
Gua I), N7-(1-hydroxy-3-buten-2-yl)-guanine (EB-Gua II), N7-(trihydroxybutyl) guanine (THB-
Gua), and bis-N7G-butanediol cross-links (bis-N7G-BD). These N7-guanine adducts are
hydrolytically labile and are slowly released from DNA to give apurinic sites. Our studies within
the previous funding period have detected measurable amounts of EB-Gua and THB-Gua
adducts in untreated cells, laboratory animals, and humans with no known exposure to BD. We
have also shown that EB-Gua adducts can be spontaneously converted to stable 2-hydroxy-3,4-
epoxybut-1-yl-FAPy-dG (EB-FAPy) adducts. The long-range goal of our research is to establish
the molecular mechanisms by which BD elicits its genotoxic and carcinogenic effects. The
objective of this research is to elucidate the metabolic/dietary origins of endogenous THB-Gua
and EB-Gua adducts and to elucidate the genotoxic effects of EB-FAPy and THB-FAPy
adducts. The central hypothesis of this research is that DNA lesions identical to those generated
by butadiene exposure can be formed by endogenous sources such as carbohydrate
metabolism. We further propose that butadiene-derived FAPy adducts contribute to
carcinogenic and mutagenic properties of butadiene. Our proposed studies will improve the
current understanding of the mechanisms of mutagenesis and cytotoxicity resulting from
butadiene exposure and afford new insights into the origins of endogenously formed DNA
lesions, reducing the uncertainty in cancer risk assessment in exposed populations.

## Key facts

- **NIH application ID:** 9961499
- **Project number:** 5R01CA100670-13
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** NATALIA Y TRETYAKOVA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $309,748
- **Award type:** 5
- **Project period:** 2003-04-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961499

## Citation

> US National Institutes of Health, RePORTER application 9961499, DNA Cross-Linking By Diepoxybutane (5R01CA100670-13). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9961499. Licensed CC0.

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