Aldehyde-Associated Mutagenesis─Current State of Knowledge

Abstract

Aldehydes are widespread in the environment, with multiple sources such as food and beverages, industrial effluents, cigarette smoke, and additives. The toxic effects of exposure to several aldehydes have been observed in numerous studies. At the molecular level, aldehydes damage DNA, cross-link DNA and proteins, lead to lipid peroxidation, and are associated with increased disease risk including cancer. People genetically predisposed to aldehyde sensitivity exhibit severe health outcomes. In various diseases such as Fanconi's anemia and Cockayne syndrome, loss of aldehyde-metabolizing pathways in conjunction with defects in DNA repair leads to widespread DNA damage. Importantly, aldehyde-associated mutagenicity is being explored in a growing number of studies, which could offer key insights into how they potentially contribute to tumorigenesis. Here, we review the genotoxic effects of various aldehydes, focusing particularly on the DNA adducts underlying the mutagenicity of environmentally derived aldehydes. We summarize the chemical structures of the aldehydes and their predominant DNA adducts, discuss various methodologies, in vitro and in vivo, commonly used in measuring aldehyde-associated mutagenesis, and highlight some recent studies looking at aldehyde-associated mutation signatures and spectra. We conclude the Review with a discussion on the challenges and future perspectives of investigating aldehyde-associated mutagenesis.

Theanine in Tea: An Effective Scavenger of Single or Multiple Reactive Carbonyl Species at the Same Time

“…The polarized carbon–oxygen (CO) double bond in the structure makes the RCS strong electrophiles, and therefore, they easily trigger aberrant modifications of deoxyribonucleic acid (DNA) and protein and cause cellular apoptosis, inflammation, and tissue injury. All of these implicate the role of the RCS in the pathogenesis of aging, obesity, and several chronic diseases . MGO and GO, as the key precursors of advanced glycation end products (AGEs), significantly contribute to the AGE pool in humans and have been considered potent protein glycation agents, triggers of oxidative stress, and novel metabolic biomarkers of cancer .…”

“…Plasma MGO and GO levels in patients with diabetes are two to six times higher than those in healthy people . ACR and CRO readily conjugate with DNA to form adducts, which are mutagenic and considered potential biomarkers of oxidative stress-related diseases and risk of cancer because they induce high mutagenicity during cell replication . ACR has been recognized as a group 3 carcinogen (“not classifiable as to its carcinogenicity to humans”) by the International Agency for Research on Cancer (IARC) and a precursor of acrylamide (a group 2 carcinogen).…”

Analysis of design criteria for biological post-treatment of ozonated wastewater treatment plant effluent

“…30 Typical organic OPB formed by the reaction of ozone with dissolved organic matter are carbonyl compounds (aldehydes, ketones), and carboxylic acids. 30 Since this group of compounds occurs at relatively high concentrations, 31 exhibits a high biodegradability, 19,32 and is associated with toxic effects, 33,34 it is highly relevant for assessing the suitability of a process for biological post-treatment. So far, approx.…”

“…The toxic effect of carbonyl compounds is attributed to the high electrophilicity of the carbonyl carbon which makes them react with nucleophilic molecules like the amino group of proteins and the nucleobases of DNA and RNA. 34,38,39 The formed covalent adducts with DNA lead to genotoxic and/or mutagenic effects. 34 The reaction with proteins may impair its target function or cause an antigen response.…”

“…34,38,39 The formed covalent adducts with DNA lead to genotoxic and/or mutagenic effects. 34 The reaction with proteins may impair its target function or cause an antigen response. 39 The short-chain aldehydes formaldehyde and acetaldehyde as well as the α-oxoaldehydes glyoxal and methylglyoxal are among the best studied compounds regarding both toxicity 33,34,40 and behaviour during ozonation/biological post-treatment.…”