Different effects of topically applied 5-fluorouracil on hairy and hairless mice

Abstract

Summary The effects of topically applied 5‐fluorouracil (5‐FU) ointment on hairy and hairless mice have been studied. Five per cent 5‐FU ointment was applied once daily to the dorsal surface of the mice, totalling one, two or seven applications. No changes have occurred in all the hairy mice, while remarkable changes such as erosion or ulcer, followed by skin hypertrophy and pigmentation have occurred after the applications of the drug to hairless mice. In the altered hairless mice, acanthosis, the appearance of active (DOPA positive) melanocytes in the epidermis and dermal cyst wall, and moderate increase in the dermal melanocytes were seen in the marked pigmentation area. Pseudocarcinomatous hyperplasia and a high increase in the dermal melanocytes were seen in the hypertrophic skin. It is suggested that different from the hairy mice skin the hairless mice skin shows abnormal reaction to 5‐FU (erosion or ulcer), resulting in epidermal hyperplasia and pigmentation.

The Mechanism of 5-Fluorouracil-Induced Hyperpigmentation in HRM-2 Hairless Mice: Focus on the Increase of Blood Vessels

“…In one study, a 5-FU ointment caused pigmentation after erosion and ulceration in hairless mice. 18) However, 5-FU systemic administration caused pigmentation, as observed in the present study, 3,6,19) suggesting a cause of pigmentation other than inflammation. In a previous study, human umbilical vein endothelial cells promoted melanogenesis by activating the melanogenic pathway in human melanocyte cells.…”

Treatment with 5-Fluorouracil and Celecoxib Displays Synergistic Regression of Ultraviolet Light B-Induced Skin Tumors

“…Although topical therapies have an advantage over surgical interventions with regard to cost, trauma, and cosmetic outcome, they too have disadvantages. Current topical chemotherapy regimens have severe side-effects, including inflammation, pain, erosion, crusting, and scarring (Tsuji et al, 1984;Gupta et al, 2001), and there is a significant risk of recurrence after treatment (Sander et al, 1997;Salim et al, 2003). Whether this is a result of compliance issues and erratic use of the drugs by the patients due to the side-effects or a low drug efficacy remains to be seen.…”

“…However, it displays variable efficacy (Ashton et al, 1970;Belisario, 1973). Topical 5-FU's utility and effectiveness are hampered by the fact that there are dramatic side-effects associated with its use, including irritation, pain, inflammation, scaling, erosion, and even scarring (Tsuji et al, 1984;Gupta et al, 2001). These side-effects and the resulting cosmetic problems often lead to sporadic use by patients, which can be a detriment to the potency of this drug.…”