phosphorus-radioisotopes and Psoriasis

Previously, we have reported a defect in the cAMP-dependent protein kinases (cAMP-PK) in psoriatic cells (i.e., a decrease in 8-azido-[32P]cAMP binding to the regulatory subunits and a decrease in phosphotransferase activity) which is rapidly reversed with retinoic acid (RA) treatment of these cells. This led us to examine a possible direct interaction between retinoids and the RI and RII regulatory subunits through retinoylation. Retinoylation of RI and RII present in normal and psoriatic human fibroblasts was analysed by [3H]RA treatment of these cells, followed either by chromatographic separation of the regulatory subunits or by their specific immunoprecipitation. These studies indicated that RI and RII can be retinoylated. [3H]RA labeling of the RII subunit was significantly (P < 0.005) greater in psoriatic fibroblasts (nine subjects; mean 7.47 relative units +/- 1.37 SEM) compared to normal fibroblasts (eight subjects; mean 2.46 relative +/- 0.49 SEM). [3H]RA labeling of and the increase in 8-azido-[32P]-binding to the RI and RII subunit in psoriatic fibroblasts showed a similar time course. This suggests that the rapid effect of retinoic acid treatment to enhance 8-azido-[32P]-cAMP binding to the RI and RII in psoriatic fibroblasts may be due, in part, to covalent modification of the regulatory subunits by retinoylation.

Topics: Affinity Labels; Autoradiography; Azides; Blotting, Western; Cell Fractionation; Chromatography; Cyclic AMP; Cyclic AMP-Dependent Protein Kinase Type II; Cyclic AMP-Dependent Protein Kinases; Fibroblasts; Humans; Phosphorus Radioisotopes; Protein Binding; Psoriasis; Skin; Time Factors; Tretinoin; Tritium

Peripheral blood lymphocytes (PBL) from psoriatic patients therapeutically exposed to polycyclic aromatic hydrocarbons (PAH) during coal tar (CT) treatment were used to evaluate the in vivo formation of benzo[a]pyrene diol epoxide(BaPDE)-DNA adducts by an ELISA technique and by the 32P-postlabeling method. Moreover, we controlled if the pretreatment with CT influences the formation of BaP-DNA adducts and the BaP metabolism in the PBL obtained from psoriatic patients, treated in vitro with BaP. Our data did not show any significant influence of the CT treatment on the levels of PAH-DNA adducts. Moreover, the use of PBL from psoriatic patients, treated in vitro with BaP, did not allow to detect significant modifications of the metabolic activation of BaP and of the ability of its metabolites to bind to DNA, before and after CT treatment. Thus, PBL do not seem to represent an useful cell model to evaluate the possible genotoxic effect of the exposure through the skin of psoriatic patients to the PAH contained in CT.

Topics: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Adolescent; Adult; Aged; Coal Tar; DNA Adducts; Enzyme-Linked Immunosorbent Assay; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Phosphorus Radioisotopes; Polycyclic Compounds; Psoriasis

Coal tar, a tumour initiator, and dithranol, a tumour promoter, are used in the treatment of psoriasis. Topical treatment of mice with pharmaceutical formulations of these two agents, at therapeutic doses, induced skin papillomas in a classical two-stage carcinogenesis protocol, while treatment with either agent alone did not. This finding has implications for the use of both agents in combination in the treatment of psoriasis.

Topics: Adenosine Triphosphate; Administration, Topical; Animals; Anthralin; Benzo(a)pyrene; Carcinogens; Coal Tar; DNA; DNA, Neoplasm; Female; Mice; Ointments; Phosphorus Radioisotopes; Psoriasis; Skin Neoplasms

A clinical therapy for psoriasis, a hyperproliferative disease of the skin, utilizes topical application of crude coal tar sometimes followed by UV irradiation (Goeckerman therapy). To investigate the formation of covalent DNA adducts resulting from this therapy, skin biopsies were obtained from treated patients and controls. Indirect immunofluorescence staining with antisera generated against benzo(a)pyrene diol epoxide-modified DNA was used to investigate cell-specific localization of adduct formation. Specific nuclear staining was detected in the epidermal cells of all biopsies from treated patients but not from control biopsies obtained from untreated individuals. 32P postlabeling of DNA isolated from the biopsies was used to determine the spectrum of hydrophobic adducts present. A pattern of multiple adducts was detected in the samples obtained from the treated patients but not from controls.

Topics: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Biopsy; Carcinogens; Coal Tar; DNA; DNA Adducts; Fluorescent Antibody Technique; Humans; Phosphorus Radioisotopes; Psoriasis; Skin

Topics: Autoantibodies; Enzyme-Linked Immunosorbent Assay; Humans; Methionine; Phosphorus Radioisotopes; Psoriasis; Raynaud Disease; Ribonucleoproteins; Ribonucleoproteins, Small Nuclear

Systemic mastocytosis occurred as a fatal event in a patient with long-standing polycythemia vera. The patient had been treated over the course of 21 yr with radioactive phosphorus. Possible relationships between mastocytosis and polycythemia vera, and also between mastocytosis and treatment with ionizing radiation, are discussed. Histopathologic and electron microscopic findings are illustrated. Difficulties in establishing the diagnosis of mast cell disease in this setting are also described.

Topics: Biopsy; Gastrointestinal Hemorrhage; Humans; Liver; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Postoperative Complications; Psoriasis; Splenectomy; Splenomegaly; Urticaria Pigmentosa