Journal Article

Metabolism and biomarkers of heterocyclic aromatic amines in humans

Turesky, Robert J., Bellamri, Medjda, Walmsley, Scott J.

2021

Overview

Heterocyclic aromatic amines (HAAs) form during the high-temperature cooking of meats, poultry, and fish. Some HAAs also arise during the combustion of tobacco. HAAs are multisite carcinogens in rodents, inducing cancer of the liver, gastrointestinal tract, pancreas, mammary, and prostate glands. HAAs undergo metabolic activation by N-hydroxylation of the exocyclic amine groups to produce the proposed reactive intermediate, the heteroaryl nitrenium ion, which is the critical metabolite implicated in DNA damage and genotoxicity. Humans efficiently convert HAAs to these reactive intermediates, resulting in HAA protein and DNA adduct formation. Some epidemiologic studies have reported an association between frequent consumption of well-done cooked meats and elevated cancer risk of the colorectum, pancreas, and prostate. However, other studies have reported no associations between cooked meat and these cancer sites. A significant limitation in epidemiology studies assessing the role of HAAs and cooked meat in cancer risk is their reliance on food frequency questionnaires (FFQ) to gauge HAA exposure. FFQs are problematic because of limitations in self-reported dietary history accuracy, and estimating HAA intake formed in cooked meats at the parts-per-billion level is challenging. There is a critical need to establish long-lived biomarkers of HAAs for implementation in molecular epidemiology studies designed to assess the role of HAAs in health risk. This review article highlights the mechanisms of HAA formation, mutagenesis and carcinogenesis, the metabolism of several prominent HAAs, and the impact of critical xenobiotic-metabolizing enzymes on biological effects. The analytical approaches that have successfully biomonitored HAAs and their biomarkers for molecular epidemiology studies are presented.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Amines / Amino acids / Aromatic amines / Biological effects / Biological markers / Biomarkers / Biomedical and Life Sciences / Biomedicine / Cancer / Carcinogenesis / Carcinogens / Cooked meat / Cooking / Creatinine / Cytotoxicity / Deoxyribonucleic acid / DNA / DNA adducts / DNA damage / Epidemiology / Fishes / Gastrointestinal system / Gastrointestinal tract / Genes / Genotoxicity / Health risks / Heterocyclic aromatic amines / Heterocyclic compounds / High temperature / Human Genetics / Hydroxylation / Intermediates / Life Sciences / Liver cancer / Meat / Metabolic activation / Metabolic rate / Metabolism / Metabolites / Mutagenesis / Mutagens / Mutation / Oncology, Experimental / Pancreas / Physiological aspects / Poultry / Prostate / Protein adducts / Review / Salmonella / Tobacco / Tumors