Human T lymphocytes bioactivate heterocyclic aromatic amines by forming DNA adducts

In this study, we investigated the ability of human T lymphocytes activated with PMA/Ionomycin or CD3/CD28 to express functional CYP1 activity and bioactivate three major HAA: 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx), and 2‐amino‐9H‐pyrido[2,3‐b]indole (AαC) to form DNA adducts. Adducts were measured by ultraperformance liquid chromatography‐electrospray ionization/multistage scan mass spectrometry. The highest level of DNA adducts occurred for AαC (16 adducts per 109 nucleotides), followed by PhIP (9 adducts per 109 nucleotides). In contrast, DNA adducts formed from MeIQx and the structurally related aromatic amine 4‐aminobiphenyl, a known human carcinogen, were below the limit of detection (< 3 adducts per 109 nucleotides). Moreover, we demonstrate that AαC is a potent inducer of CYP1A1 and CYP1B1 activity through a transcriptional mechanism involving the AhR pathway. Overall, our results highlight the capacity of activated human T lymphocytes to more efficiently bioactivate AαC to form DNA adducts than other prominent HAA or 4‐ABP. Environ. Mol. Mutagen., 2016. © 2016 Wiley Periodicals, Inc.
Source: Environmental and Molecular Mutagenesis - Category: Molecular Biology Authors: Tags: Research Article Source Type: research