Catharina M. Lerche

Topical tacrolimus in combination with simulated solar radiation does not enhance photocarcinogenesis in hairless mice.

Abstract:u2002 Numerous studies have demonstrated the utility of topical tacrolimus ointment in atopic dermatitis. However, there is a concern that local immunosuppression by calcineurin inhibitors may enhance dermal photocarcinogenesis and carcinogenesis. Therefore, we investigated the influence of topical tacrolimus ointment on squamous cell carcinoma formation in hairless female C3.Cg/TifBomTac immunocompetent mice exposed to solar simulated radiation (SSR). In a first experiment, mice (nu2003=u2003200) had tacrolimus applied on their dorsal skin three times weekly followed by SSR (2, 4 or 6 standard erythema doses, SED) 3–4u2003h later. Tacrolimus did not reduce the time to tumor development and in the group receiving 4 SED it even had a protective effect (156u2003days vs 170u2003days, Pu2003=u20030.008). In a second experiment, mice (nu2003=u200350) were irradiated with 6 SED three times weekly for 3u2003months and subsequently treated five times weekly with topical tacrolimus to mimic the use of tacrolimus on sun‐damaged skin. The median time to the first skin tumor was 234u2003days in SSRu2003+u2003tacrolimus group compared with 227u2003days in the only SSR‐irradiated group (Pu2003=u20030.160). In a third experiment, mice (nu2003=u200325) had tacrolimus applied on their dorsal skin every day for 1u2003month, thereafter the group was irradiated with 4 SED three times weekly. The median time to the first skin tumor was 142u2003days in tacrolimusu2003+u2003SSR group compared with 156u2003days in the only SSR‐irradiated group from experiment 1 (Pu2003=u20030.363). We conclude that tacrolimus ointment does not accelerate photocarcinogenesis or induce any dermal carcinogenicity in hairless mice.

Topical pimecrolimus and tacrolimus do not accelerate photocarcinogenesis in hairless mice after UVA or simulated solar radiation.

Abstract:u2002 Pimecrolimus and tacrolimus are topical calcineurin inhibitors developed specifically for the treatment of atopic eczema. Experience with long‐term use of topical calcineurin inhibitors is limited and the risk of rare but serious adverse events remains a concern. We have previously demonstrated the absence of carcinogenic effect of tacrolimus alone and in combination with simulated solar radiation (SSR) on hairless mice. The aim of this study is to determine whether pimecrolimus accelerates photocarcinogenesis in combination with SSR or pimecrolimus and tacrolimus accelerate photocarcinogenesis in combination with UVA. We used 11 groups of 25 hairless female C3.Cg/TifBomTac immunocompetent mice (nu2003=u2003275). Pimecrolimus cream or tacrolimus ointment was applied on their dorsal skin three times weekly followed by SSR (2, 4, or 6 standard erythema doses, SED) or UVA (25u2003J/cm2) 3–4u2003h later. This was done up to 365u2003days in the SSR‐treated groups and up to 500u2003days in the UVA‐treated groups. Pimecrolimus did not accelerate the time for development of the first, second or third tumor in any of the groups. Median time to the first tumor was 240u2003days for the control‐2SED group compared with pimecrolimus‐2SED group (233u2003days), control‐4SED group (156u2003days) compared with pimecrolimus‐4SED group (163u2003days) and control‐6SED group (162u2003days) compared with pimecrolimus‐6SED group (170u2003days). Only one mouse in each of the three UVA groups developed a tumor. We conclude that pimecrolimus in combination with SSR and both pimecrolimus and tacrolimus in combination with UVA do not accelerate photocarcinogenesis in hairless mice.

Photocarcinogenesis and toxicity of benzoyl peroxide in hairless mice after simulated solar radiation

Please cite this paper as: Photocarcinogenesis and toxicity of benzoyl peroxide in hairless mice after simulated solar radiation. Experimental Dermatology 2009;

Topical hydrocortisone, clobetasol propionate, and calcipotriol do not increase photocarcinogenesis induced by simulated solar irradiation in hairless mice

Please cite this paper as: Topical hydrocortisone, clobetasol propionate, and calcipotriol do not increase photocarcinogenesis induced by simulated solar irradiation in hairless mice. Experimental Dermatology 2010; 19: 973–979.

High death rate in mice treated topically with diclofenac

Abstract:u2002 Recently, 3% diclofenacnatrium gel (diclofenac) was introduced for the treatment of actinic keratoses. Data on photocarcinogenesis of topical diclofenac are limited, and we wished to investigate whether topical diclofenac can accelerate photocarcinogenesis using simulated solar radiation (SSR). Diclofenac was applied topically on the backs of hairless, female, C3.Cg/TifBomTac immunocompetent mice three times weekly followed by ultraviolet radiation (2, 3, or 4 Standard Erythema Dose) until death. There was a significant difference in survival between diclofenac‐treated groups and control groups (Pu2003<u20030.0001). Physical examination of the diclofenac‐treated mice showed peptic ulcers, oesophageal ulcers and gastrointestinal bleeding. To be sure that these side effects were not caused by topical absorption without oral ingestion, one group of mice was wearing Elizabethian collars and was single housed. Nevertheless, these mice also had gastrointestinal side effects. We terminated the experiment after 151u2003days when only a few mice remained in the diclofenac‐treated groups and most had symptoms of discomfort and weight loss. No tumors developed as a result of the early termination.

Black tattoos protect against UVR-induced skin cancer in mice.

Black tattoos may involve risk of cancer owing to polycyclic aromatic hydrocarbons including benzo(a)pyrene (BaP) in inks. Ultraviolet radiation (UVR) induces skin cancer. The combination of UVR and black tattoo may therefore potentially be very problematic, but has not been previously studied.

X-rays and photocarcinogenesis in hairless mice

It is well known that excessive X-ray radiation can cause non-melanoma skin cancers. With the increased incidence of sun-related skin cancer there is a need to investigate the combination of sunlight and X-rays. Immunocompetent C3.Cg/TifBomTac mice (nxa0=xa0298) were divided into 12 groups. Mice were irradiated with 12, 29 or 50xa0kV X-rays. The mice received a total dose of 45xa0Gy. They were irradiated with 3 SED simulated solar radiation (SSR) either before or after irradiation with X-rays. The groups irradiated with X-rays alone, 0, 3, 9 and 10 mice (0, 12, 29 and 50xa0kV, respectively) developed squamous cell carcinoma. In the groups irradiated with SSR after X-rays the development of tumours was significantly faster in the 50xa0kV group than in the corresponding control group (175 vs. 194xa0days, pxa0<xa00.001). In the groups irradiated with SSR prior to the X-ray radiation the development of tumours was significantly faster in the 29 and the 50xa0kV groups than in the corresponding control group (175 vs. 202xa0days, pxa0<xa00.001 and 158 vs. 202xa0days, pxa0<xa00.001, respectively). In conclusion, X-ray radiation alone is a weak carcinogen in hairless mice. There is an added carcinogenic effect if X-ray radiation is given on prior sun-exposed skin or if the skin is sun-exposed after X-rays. We still believe that X-ray radiation is a safe and effective therapy for various dermatological diseases but caution should be observed if a patient has severely sun-damaged skin or has a high-risk sun behaviour.

Neonatal mice do not have increased sensitivity to induction of squamous cell carcinomas

Squamous cell carcinoma (SCC) is linked with the lifelong cumulative effect of ultraviolet radiation (UVR). In contrast, epidemiological data have shown that sunburn in childhood is a stronger risk factor for cutaneous malignant melanoma than continuous UVR, indicating a higher carcinogenic sensitivity early in life.

Reduced ultraviolet irradiation delays subsequent squamous cell carcinomas in hairless mice

Background: Ultraviolet (UV) radiation induces non‐melanoma skin cancer (NMSC), and UV prophylaxis is essential to prevent skin cancer. It is unclear whether patients diagnosed with squamous cell carcinomas (SCC) may benefit from reduced UV exposures in terms of delaying the development of new tumors. The objective was to evaluate the significance of discontinued or reduced UV exposure for the development of subsequent skin tumors.

Tattoo Pigments Are Observed in the Kupffer Cells of the Liver Indicating Blood-Borne Distribution of Tattoo Ink

Aim: Tattoo pigments are deposited in the skin and known to distribute to regional lymph nodes. Tattoo pigments are small particles and may be hypothesized to reach the blood stream and become distributed to peripheral organs. This has not been studied in the past. The aim of the study was to trace tattoo pigments in internal organs in mice extensively tattooed with 2 different tattoo ink products. Material/Methods: Three groups of mice were studied, i.e., 10 tattooed black, 10 tattooed red, and 5 untreated controls. They were tattooed on the entire back with commercial tattoo inks, black and red. Mice were sacrificed after 1 year. Samples were isolated from tattooed skin, lymph nodes, liver, spleen, kidney, and lung. Samples were examined for deposits of tattoo pigments by light microscopy and transmission electron microscopy (TEM). Results: TEM identified intracellular tattoo pigments in the skin and in lymph nodes. TEM in both groups of tattooed mice showed tattoo pigment deposits in the Kupffer cells in the liver, which is a new observation. TEM detected no pigment in other internal organs. Light microscopy showed dense pigment in the skin and in lymph nodes but not in internal organs. Conclusion: The study demonstrated black and red tattoo pigment deposits in the liver; thus, tattoo pigment distributed from the tattooed skin via the blood stream to this important organ of detoxification. The finding adds a new dimension to tattoo pigment distribution in the body, i.e., as observed via the blood in addition to the lymphatic pathway.