Irinotecan-Induced Site-Specific Pigmentation in the Plantar Region of Mice

Abstract

Skin pigmentation is a widely recognized side effect of cancer chemotherapy that can negatively affect patient QOL. However, although numerous case reports have documented pigmentation caused by anticancer drugs, the precise mechanisms remain unclear. Among such pigmentation, that induced by 5-fluorouracil (5-FU) has garnered considerable attention, whereas reports on irinotecan-induced pigmentation are comparatively limited. In this study, we investigated the pigmentation-related effects of irinotecan in colored hairless mice. Mice received intraperitoneal injections of 20 mg/kg irinotecan, and we subsequently examined the pigmentation of the plantar and buttock regions. The results indicated that irinotecan specifically induces pigmentation in the plantar region, with no pigmentation observed on the buttocks. In contrast, pigmentation was noted on the buttocks, although not in the plantar region, in the control mice treated with 5-FU and cytarabine. Furthermore, irinotecan treatment promoted a marked elevation in the expression of tyrosinase, cAMP response element binding protein (CREB), and microphthalmia-associated transcription factor (MITF) in the plantar region, whereas no significant changes were observed in the buttocks. These findings indicate that irinotecan leads to site-specific pigmentation in the sole of the foot, thereby highlighting the potential for anticancer drugs to cause localized pigmentation.