DNA Damage by Endogenous and Exogenous Aldehydes

Marisa Medeiros

doi:10.21577/0103-5053.20190056

Abstract

The present overview describes the formation of deoxyribonucleic acid (DNA) adducts from endogenous and exogenous aldehydes, such as acetaldehyde, acrolein, crotonaldehyde, malonaldehyde, 4-hydroxy-2-nonenal and 2,4-decadienal. Malonaldehyde reacts with 2’-deoxyguanosine, 2’-deoxyadenosine, and 2’-deoxycytidine, yielding cyclic pyrimidopurinone and acyclic adducts. The direct addition of ɑ,β-unsaturated aldehydes to DNA bases yields cyclic substituted propano adducts, such as 1,N2-propano-2’-deoxyguanosine. Alternatively, ɑ,β-unsaturated aldehydes can be oxidized to reactive epoxides, giving ethano or etheno derivatives upon reaction with DNA. In addition, information on highly sensitive techniques, employed for the in vivo detection and quantification of DNA-aldehyde adducts, is also provided. Some of these DNA-aldehyde lesions have been shown to be highly mutagenic. In fact, lipid peroxidation and exogenous aldehyde exposure could potentially account for the observed carcinogenicity of urban air pollution and cigarette smoke exposure.

Highlights

The integrity and stability of genetic information is crucial for maintaining life
By the lipid peroxidation, which produces a large number of reactive aldehydes
Many of these aldehydes react with biomolecules such as deoxyribonucleic acid (DNA), proteins and amino acids, resulting in a variety

Summary

Introduction

The integrity and stability of genetic information is crucial for maintaining life. deoxyribonucleic acid (DNA) is not inert and has numerous sites for chemical interaction. Aldehydes are known to react with and modify DNA These compounds are widespread in the environment, and are present in foods, beverages, cigarette smoke, and are formed through the combustion of wood, coal, alcohol and diesel fuels.[3] Exogenous aldehydes, such as acrolein, 2,4-nonadienal and 2-pentenal, are formed during the cooking of fats, oils, and sugars.[4] Aldehydes are produced endogenously, primarily, by the lipid peroxidation, which produces a large number of reactive aldehydes. Many of these aldehydes react with biomolecules such as DNA, proteins and amino acids, resulting in a variety. It is important to note that air pollution was classified by the International Agency for Research on Cancer (IARC) as carcinogenic to humans (IARC Group 1).[7]

The Lipid Peroxidation Process

Aldehyde-DNA Adducts

Endogenous and Exogenous Acetaldehyde

DNA-Adducts Quantification in vivo

Mechanism of in vivo Aldehyde Detoxification

Conclusions