Untreated Mouse Skin Research Articles

Alpha-hydroxy acids: Consideration of the biological effects and possible role in photocarcinogenesis

The U.S. Food and Drug Administration nominated topically applied alpha-hydroxy acids to the U.S. National Toxicology Program for toxicological studies. The alpha-hydroxy acids are present at significant concentrations in many cosmetic products and are marketed as products to correct photoaging of skin. In this paper, we review the current knowledge concerning the effect of topical treatment of mice with creams containing alpha-hydroxy acids and the effect of ultraviolet radiation on treated and untreated mouse skin.

ATX-S10(Na)-photodynamic therapy is less carcinogenic for mouse skin compared with ultraviolet B irradiation

Photodynamic therapy (PDT) is available for the treatment of various skin tumours and other skin diseases. Ultraviolet (UV) irradiation induces DNA damage, cyclobutane pyrimidine dimers (CPD) (6-4) photoproducts (6-4PP) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), all of which are carcinogenic for the skin. However, effects of PDT on DNA damage and carcinogenesis are unclear. To compare the production of photoproducts and the induction of skin tumours in mouse epidermis treated with UVB or PDT. We performed UVB irradiation or ATX-S10(Na)-PDT on the skin of 20 hairless mice, in each case, and analysed DNA damage and tumour induction. After a single irradiation of UVB on mouse skin, CPD, 6-4PP and 8-OHdG were detected in the nuclei of keratinocytes. In contrast, PDT-treated mouse keratinocytes showed induction of 8-OHdG, but not of CPD or 6-4PP. Skin tumours induced by UVB irradiation (3 kJ m(-2) three times weekly) were observed following 15 weeks of irradiation (mean +/- SEM tumour incidence 3.2 +/- 1.8%; tumour number 3.2 +/- 1.6 per mouse) and increased depending on irradiation times and doses. Following 30 weeks of UVB irradiation (3 kJ m(-2) three times weekly), mean +/- SEM tumour incidence and tumour number were 28.7 +/- 4.8% and 14.2 +/- 2.8% per mouse, respectively. Although skin tumours were also detected in PDT-treated mouse skin following 80 weeks of treatment (mean +/- SEM tumour incidence 9.1 +/- 1.8%; tumour number 12.2 +/- 2.3 per mouse), the number of tumours was not statistically different from untreated mouse skin (mean +/- SEM tumour incidence 4.1 +/- 3.8%; tumour number 5.2 +/- 3.3 per mouse). PDT induced 8-OHDG but not CPD or 6-4PP, and was shown to be a relatively safe modality following multiple applications to mouse skin.

Substrate specificity of the mouse skin mixedfunction oxidase system

The metabolism of nine model substrates for the mixed-function oxidase system was studied in skin and liver microsomes from Balb/C mice. Rates of skin metabolism per mg microsomal protein ranged from 0.5-15% of liver rates depending on the substrate. Relative to liver, mouse skin preferentially metabolized ethoxyresorufin, benzo[alpha]pyrene and diphenyloxazole over aldrin, coumarin and the C1-C4 7-alkyl umbelliferone ethers. NADPH-cytochrome P-450-dependent metabolism of aldrin and ethoxyresorufin was differentially inhibited in skin microsomes by metyrapone and alpha-naphthoflavone, respectively. Biphasic Eadie-Hofstee plots were obtained in both skin and liver microsomes for the metabolism of aldrin, whereas metabolism of ethoxyresorufin in both systems was described by linear kinetics. It is concluded that mouse skin contains multiple forms of cytochrome P-450, and that forms functionally analogous to those induced by polycyclic hydrocarbons in rodent liver are present in untreated mouse skin.

Histogenesis of the intradermal melanocytic tumor in BDF1 mice induced by topical application of 9,10-dimethyl-1,2-benzanthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA).

The histogenesis of the intradermal melanocytic tumor induced in the skin of 88 female BDF1 mice by DMBA and TPA is studied light-and electron-microscopically. Four types of melanocytes were found in the mouse skin. The epidermal melanocytes transiently appeared several days after topical application of DMBA. Hair follicles turned into anagen phase and follicular melanocytes became apparent by week 3. After week 3, intradermal melanocytes of the perifollicular melanocytic networks (PFM), which were scattered in untreated mouse skin, proliferated to form the intradermal melanocytic tumors, and 267 tumors, composed of oval melanocytes in medullary growth, were induced in all of the 19 treated mice by week 32. Large dendritic melanocytes located deep in the reticular dermis, which did not participate in the formation of the tumor. Only 3 papillomas were induced in 2 of the 19. Light-and electron-microscopically, there was no evidence of migration of epidermal and hair follicular melanocytes into the dermis. Additionally, melanin-producing activity in the cytoplasm of Schwann cell and perineural epithelium was observed. The histogenesis of the intradermal melanocytic tumor was closely related to the melanocytes of the perifollicular melanocytic network (PFM).

Skin-SH levels of mice.

DURING the examination of changes in the soluble sulphydryl content of mouse skin produced by application of polycyclic hydrocarbons it was noted that the result from a sample (pool of two animals) taken from a larger group occasionally differed significantly from the mean —SH for the larger group. The possibility existed that those animals the skin —SH of which differed from the mean were of different age or had skin with hair in more than one stage of growth. Consequently, untreated mouse skin from mice of varying age, sex, strains, and stage of hair cycle were used to investigate factors determining soluble sulphydryl content of mouse skin.