Metabolism and biomarkers of heterocyclic aromatic amines in humans

Abstract

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.

Establishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids

“…It has also been reported that DNA adducts, such as spiroiminohydantoin and guanidine hydantoin produced by further oxidation of 8-OH-dG, are involved in the induction of G:C > C:G transversion ( Kino and Sugiyama, 2001 ; Kornyushyna et al, 2002 ). Additionally, DNA strand breaks and 8-oxo-dG formation are induced during dG-C8-arylamine adduct formation via rearrangement of dG-N7-arylamine hydrazine adducts ( Bellamri et al, 2021 ). Based on these chemical mechanisms, G:C to C:G transversion and deletion may be increased by PhIP exposure in vivo and in vitro .…”

“…In this mouse model, point mutations and deletions are analyzed by gpt and Spi-selections, respectively, and are widely used in the field of environmental mutagenicity, including 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) and acrylamide (AA) (Figure 1) (Masumura et al, 1999;Masumura et al, 2000;Ishii et al, 2015). Both chemicals are known as foodborne carcinogens and are responsible for the development of some human cancers (de Conti et al, 2019;Adani et al, 2020;Bellamri et al, 2021;Le Marchand, 2021). Moreover, PhIP is produced by Maillard reactions between glucose, phenylalanine, and creatinine and is the most abundant heterocyclic amine produced during the cooking of meat and fish (Felton et al, 2000).…”

“…In F344 rats, PhIP can induce tumors in the colon and prostate in males, and in the mammary glands of female rats. It also induced colon tumors in the dextran sulphate sodium-induced colitis mouse model ( Tanaka et al, 2005 ; Bellamri et al, 2021 ). In contrast, AA is produced by the heating of carbohydrate-rich foods such as potatoes at high temperatures.…”

Bioinformatic Analysis Identified Hub Genes Associated with Heterocyclic Amines Induced Cytotoxicity of Peripheral Blood Mononuclear Cells

“…Heterocyclic amines (HCAs) are potential mutagens ubiquitously existing in cooked protein-rich food such as fried fish and roasted meat [ 1 ]. Hiding behind the tempting flavor and rich nutrients of grilled food, HCAs are inevitably consumed by and absorbed into human bodies and exert toxicological effects [ 2 ]. Studies have found several kinds of HCAs.…”

Presentation1.pdf

“…In F344 rats, PhIP can induce tumors in the colon and prostate in males, and in the mammary glands of female rats. It also induced colon tumors in the dextran sulphate sodiuminduced colitis mouse model (Tanaka et al, 2005;Bellamri et al, 2021). In contrast, AA is produced by the heating of carbohydrate-rich foods such as potatoes at high temperatures.…”