Background: Despite its widespread use in acne vulgaris treatment, the potential cytological and genotoxic effects of systemic isotretinoin on oral mucosal cells remain poorly understood. This study aimed to investigate the cytological and genotoxic effects of systemic isotretinoin on oral mucosal cells.
Methods: Buccal smear samples were collected from isotretinoin users (n = 20) and controls (n = 20). Cytomorphometric analyses (cell diameter (CD), nuclear diameter (ND), nuclear area (NA), cell area (CA), ND/CD, and NA/CA ratios) and cytological evaluations (nuclear degenerations, binucleation, perinuclear halos) were conducted using Papanicolaou staining. Micronucleus (MN) testing was performed on Feulgen-stained samples.
Results: CD, ND, CA, and NA were significantly higher in the isotretinoin group (p < 0.05), while the ND/CD ratio was reduced (p < 0.05). MN scores and the presence of micronucleated cells (MNed cells) were significantly increased in isotretinoin users (p < 0.05), indicating genotoxic effects. The isotretinoin group showed a lower mean pH (5.8) than controls (6.7) (p < 0.001). No significant differences were linked to isotretinoin duration (less than 6 months (6<) vs. 6 months or more (6≥)) (p > 0.05).
Conclusions: Isotretinoin use induces cytological changes, including increased cell and nuclear sizes, and genotoxic effects, as evidenced by elevated MN formation. Monitoring oral mucosal alterations in isotretinoin users may provide insights into potential side effects.
Keywords: acne vulgaris; buccal smear; isotretinoin; micronucleus; oral mucosa.
© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.