DNA Damage by Endogenous and Exogenous Aldehydes

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 α,β-unsaturated aldehydes to DNA bases yields cyclic substituted propano adducts, such as 1,N 2 -propano-2'-deoxyguanosine. Alternatively, α,βunsaturated 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.

Differential Responses to Bioink-Induced Oxidative Stress in Endothelial Cells and Fibroblasts

“…In both NIH/3T3 and EA.hy926 cells, there was a concentration-dependent effect of oxidation degree on cell viability, with the strongest cytotoxicity observed at the highest DO of 26% after 72 h of culture. It is known from the literature that CHO-groups may be responsible for cytotoxicity [ 31 , 45 ]. Besides certain alterations in material properties, e.g., viscosity and chain length, the main difference between alginate and ADA hydrogels resulting from the treatment with NaIO 4 was the formation of CHO groups.…”

“…In this study, we hypothesized that free aldehyde groups in the hydrogel could be responsible for reduced cell viability and can elicit a cell type-specific reaction. Exogenous aldehydes can stress cells and lead to DNA damage through oxidative stress [ 31 , 32 ]. At the cellular level, this oxidative stress can result in a wide range of responses such as inhibition of proliferation, growth arrest or even cell death.…”

The skin redoxome

“…Accumulation of ReAS can cause lipid peroxidation, formation of reactive aldehydes (Fig. 4) and the lipid peroxidation end products (ALEs), represented by Lipofuscin, for example, 93,94 which are prone to react with other molecules forming the so-called advanced glycation end products (AGEswhose key biomarker is N(6)-carboxymethyllysine), 95,96 protein carbonylation 97 and modification of nitrosylation of tyrosine residues forming nitrotyrosine 98 DNA can also form adducts with reactive aldehydes, which can be highly mutagenic 99 (Fig. 4).…”

Effect of episomally encoded DNA polymerases on chemically induced mutagenesis at the hisG46 target in Ames test

“…The propano-adduct forming lipid peroxidation products such as crotonaldehyde and 4-hydroxy-2-nonenal have been implicated in carcinogenesis in multiple studies [40,[43][44][45] and are even considered to be the principal carcinogens after the exposure to other environmental mutagens such as AFB1, urban air pollution, alcohol and cigarette smoke [41,46,47] or during wok cooking [48]. For instance crotonaldehyde is according to IARC considered only as a Class 3 human carcinogen [49] but it is likely the principal carcinogen after the exposure to the Class 1 human carcinogen acetaldehyde [47,50,51] or pYG8524 pBR322 derivative expressing the activated MucA' subunit of PolRI from the lac promoter [19] pYG8529 pBR322 derivative expressing the activated SamA' polymerase subunit from the lac promoter [19] pYG8517 pSC101 derivative expressing the MucB catalytic subunit of PolRI from the lac promoter [19] pYG8518 pSC101 derivative expressing the SamB polymerase subunit from the lac promoter [19] Km r resistant to kanamycin, Cm r resistant to chloramphenicol, Tc r resistant to tetracycline, Ap r resistant to ampicillin Class 2B human carcinogen N-nitrosopyrrolidine [52].…”