Genotoxic Agents: An Unexpected Effect on Healthy Epithelia

The study revealed that DNA cross-linking agents, commonly used in cancer treatment, unexpectedly induced hyperplasia and stem cell fate mis-specification in healthy epithelial tissues such as skin, mammary glands, and hair follicles. This effect was mediated by inflammasome activation and IL-1β production in dermal fibroblasts, rather than a direct response of the epithelial cells themselves. The findings suggested that fibroblasts play a crucial role in this process by secreting factors that affect keratinocytes. The study highlighted potential risks of long-term use of these agents, including continuous hyperproliferation and increased cancer recurrence, necessitating further research to understand the implications for human treatments.