Related Experiment Videos
Dithranol (anthralin)-induced skin irritation in C57BL/6, NMRI and SENCAR mice
1Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Abstract:
Dithranol-induced skin irritation was compared in C57BL/6, NMRI and SENCAR mice, the strains representing different sensitivity to tumour promotion. Skin irritation was assessed using ear thickness and skin weight measurements, visual estimation of back skin irritation and histopathology. Both single and repeated applications of dithranol caused a delayed skin irritation resulting in the maximal response between 7-11 days after the beginning of the treatment. Contrary to the findings with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), C57BL/6 mice were the most sensitive and SENCAR mice the most resistant to the dithranol-induced skin irritation up to 30 days from the beginning of the treatment. NMRI mice were intermediate. Differences were found in the ear swelling, epidermal hyperplasia, amount of inflammatory cell infiltrate and skin ulceration. During repeated treatment of about 40 days, however, the responsiveness of SENCAR mice increased over that of C57BL/6 and NMRI mice. SENCAR mice had also more epidermal hyperplasia than the other strains at the end of the 74 day period of 3 times weekly applications. The magnitude of epidermal hyperplasia after long term treatment seems to correlate with the sensitivity to tumor promotion in the different mouse strains.
Insights
Dithranol causes delayed skin irritation in mice, with C57BL/6 strains being most sensitive initially. However, SENCAR mice show increased responsiveness and epidermal hyperplasia with prolonged dithranol treatment, correlating with tumor promotion sensitivity.
Area of Science:
- Toxicology
- Dermatology
- Carcinogenesis
Background:
- Dithranol is a topical irritant used in treating psoriasis.
- Mouse models are crucial for understanding skin responses to chemical irritants and tumor promoters.
- Different mouse strains exhibit varying sensitivities to chemical-induced skin conditions.
Purpose of the Study:
- To compare the sensitivity of C57BL/6, NMRI, and SENCAR mouse strains to dithranol-induced skin irritation.
- To investigate the relationship between dithranol-induced skin responses and sensitivity to tumor promotion.
Main Methods:
- Dithranol was applied to mouse skin (C57BL/6, NMRI, SENCAR) to assess irritation.
- Measurements included ear thickness, skin weight, visual scoring, and histopathology.
- Long-term studies involved repeated applications over extended periods.
Main Results:
- Dithranol induced a delayed skin irritation peaking 7-11 days post-application.
- C57BL/6 mice were initially most sensitive, while SENCAR mice were most resistant to dithranol irritation.
- With prolonged treatment, SENCAR mice showed increased responsiveness and epidermal hyperplasia, correlating with tumor promotion sensitivity.
Conclusions:
- Mouse strain sensitivity to dithranol-induced skin irritation varies and differs from TPA response.
- Long-term dithranol exposure in SENCAR mice leads to enhanced skin responses, suggesting a link to tumor promotion susceptibility.