N-acetyltransferase metabolism and DNA damage following exposure to 4,4’-oxydianiline in human bronchial epithelial cells

• Published in: Toxicology letters 2024-07, Vol.398, p.65-68
• Main Authors: Wise, James T.F., Hein, David W.
• Format: Article
• Language: English
• Subjects: 4,4’-Oxydianiline; Acetylation; Arylamine N-Acetyltransferase - genetics; Arylamine N-Acetyltransferase - metabolism; Bronchi - cytology; Bronchi - drug effects; Bronchi - metabolism; Cell Line; DNA Damage; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Hookah smoke; Human bronchial epithelial cells; Humans; Isoenzymes; N-acetylation; Smoke - adverse effects; Waterpipe
• ISSN: 0378-4274; 1879-3169; 1879-3169
• DOI: 10.1016/j.toxlet.2024.06.005

Waterpipe smoking is increasingly popular and understanding how chemicals found in hookah smoke may be harmful to human bronchial epithelial cells is of great importance. 4,4’-Oxydianiline (ODA), is an aromatic amine which is present at comparatively high levels in hookah smoke. The metabolism and the subsequent toxicity of ODA in human bronchial epithelial cells remains unknown. Given that ODA is an aromatic amine, we hypothesized that ODA is N-acetylated and induces DNA damage following exposure to immortalized human bronchial epithelial cells (BEP2D cells). We measured the N-acetylation of ODA to mono-acetyl-ODA and the N-acetylation of mono-acetyl-ODA to diacetyl-ODA by BEP2D cells following separation and quantitation by high performance liquid chromatography. For ODA, the apparent KM in cells was 12.4 ± 3.7 µM with a Vmax of 0.69 ± 0.03 nmol/min/106 cells, while for mono-acetyl-ODA, the apparent KM was 111.2 ± 48.3 µM with a Vmax of 17.8 ± 5.7 nmol/min/106 cells ODA exposure for 24 h resulted in DNA damage to BEP2D cells following concentrations as low as 0.1 µM as measured by yH2Ax protein expression These results demonstrate that ODA, the most prevalent aromatic amine identified in hookah smoke, is N-acetylated and induces DNA damage in human bronchial epithelial cells. •4,4’-Oxydianiline (ODA) is present at comparatively high levels in hookah smoke.•N-acetylation of ODA was determined in human bronchial epithelial cells.•ODA exposure resulted in DNA damage to human bronchial epithelial cells.