Identification of acetaldehyde-DNA adducts in HepG2 cells exposed to ethanol

• Grant number: 23/05018-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2023
• Effective date (End): December 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marisa Helena Gennari de Medeiros
• Grantee: Mariana Amanda Araujo Oliveira
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

Alcohol consumption is associated with the development of several types of cancer. The mechanisms involved in this process are not fully understood, but the formation of acetaldehyde derived from ethanol seems to play an important role. In populations deficient in aldehyde dehydrogenase, high levels of acetaldehyde have been associated with an increased risk of esophageal cancer after alcohol consumption compared to populations with fully active enzyme. The formation of acetaldehyde-DNA adducts has been considered to be an important factor in the mechanism of mutagenesis and carcinogenesis. Acetaldehyde reacts with 2'-deoxyguanosine (dGuo) in DNA to primarily form N2-ethylidene-2'-deoxyguanosine (N2-ethylideneGuo), an unstable Schiff base. The subsequent reaction of N2-ethylidenedGuo with a second molecule of acetaldehyde leads to the formation of the diastereoisomers (6S, 8S) and (6R, 8R) of 1, N2-propane-2'-deoxyguanosine (1, N2-propanedGuo). O our group was one of the pioneers in detecting this adduct in cells and in vivo by exposure to acetaldehyde. This project aims to investigate whether 1, N2-propanedGuo is formed in cells exposed to ethanol at different concentrations. The use of isotopically labeled ethanol may unequivocally demonstrate the participation of this pathway in DNA modification.