A Systematic Review Investigating the Cytogenotoxic Effects of Isotretinoin

Isotretinoin (13-cis-retinoic acid) is commonly used to treat severe acne vulgaris. However, concerns remain about its potential genotoxic and cytotoxic effects. The aim of this study was to conduct a systematic review and critical analysis of the available evidence on the cytogenotoxic effects of isotretinoin. A systematic review was conducted using the PICOS framework and the PRISMA 2020 guidelines. Databases searched included PubMed, Scopus, and Web of Science up to March 2026. Studies that evaluated genotoxicity through biomarkers, such as the micronucleus assay, the comet assay, and oxidative DNA damage markers, were included. Eight studies that met the inclusion criteria were identified; these studies included in vitro, in vivo, and clinical investigations. The findings demonstrated that isotretinoin may induce DNA damage, particularly with prolonged exposure to higher concentrations, as evidenced by increased DNA strand breaks. Clinical studies reported elevated frequencies of micronuclei and oxidative DNA damage markers, such as 8-OHdG, as well as reduced antioxidant defenses. However, some studies also suggested the antigenotoxic effects of isotretinoin. The available evidence suggests that isotretinoin exhibits a complex, context-dependent genotoxic profile influenced by dose, exposure duration, and biological model. Prolonged use appears to be associated with genomic instability and oxidative stress. These findings underscore the need for future studies to evaluate risk-benefit ratios and biomonitoring strategies in clinical practice.