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Biomedical subjects

A Spinowitz

Publications and source records attributed to A Spinowitz.

5 recordsLinked to original sources

Pyrimidine dimer removal enhanced by DNA repair liposomes reduces the incidence of UV skin cancer in mice.

UV exposure has been linked to skin cancer in humans by epidemiology and the rare genetic disease xeroderma pigmentosum. However, UV produces multiple photoproducts in DNA, and their relative contribution is uncertain. An enzyme which specifically repairs cyclobutane pyrimidine dimers in DNA, T4 endonuclease V, was encapsulated in liposomes for topical delivery into mouse and human skin. In both species, liposomes applied after UV exposure localized in the epidermis and stimulated the removal of cyclobutane pyrimidine dimers. UV-irradiated mice treated with these liposomes had a dose-dependent decrease in the incidence of squamous cell carcinoma compared to controls. The results demonstrate that unrepaired cyclobutane pyrimidine dimers in DNA are a direct cause of cancer in mammalian skin.

Animals↗

Enhanced unscheduled DNA synthesis in UV-irradiated human skin explants treated with T4N5 liposomes.

Epidermal keratinocytes cultured from explants of skin cancer patients, including biopsies from xeroderma pigmentosum patients, were ultraviolet light-irradiated and DNA repair synthesis was measured. Repair capacity was much lower in xeroderma pigmentosum patients than in normal patients. The extent of DNA repair replication did not decline with the age of the normal patient. Treatment with T4N5 liposomes containing a DNA repair enzyme enhanced repair synthesis in both normal and xeroderma pigmentosum keratinocytes in an irradiation- and liposome-dose dependent manner. These results provide no evidence that aging people or skin cancer patients are predisposed to cutaneous malignancy by a DNA repair deficiency, but do demonstrate that T4N5 liposomes enhance DNA repair in the keratinocytes of the susceptible xeroderma pigmentosum and skin cancer population.

Adult↗

Chronic active hepatitis associated with etretinate therapy.

Acute hepatitis developed in a patient taking etretinate for severe psoriasis. Discontinuation of therapy was followed by progression of the histological changes to chronic active hepatitis, despite improvement of his clinical and laboratory status. This is the third reported case of chronic active hepatitis associated with etretinate therapy, and the second patient in our group of twenty-two etretinate-treated patients with severe psoriasis to develop clinically significant hepatic disease. Immunological evaluation revealed a marked increase in the patient's OKMI-staining population of peripheral mononuclear cells and augmentation of Con A-induced lymphocyte blastogenesis in the presence of etretinate.

Acute Disease↗