Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In combination with transition metals (Mn(II), Cu(II), and Fe(III)), isoniazid and related hydrazine compounds induced unscheduled DNA synthesis (DNA repair) in cultured human fibroblasts. Manganese at 10(-5) and 10(-4) M strongly enhanced DNA repair induced by isoniazid, iproniazid, nialamide and hydrazine. Peak levels of DNA repair occurred at 5 x 10(-4)--10(-3) M of the 4 hydrazine compounds. Copper caused less enhancement of DNA repair while iron had no detectable effect. Without added metal, unscheduled DNA synthesis was not observed in cells treated with any of the 4 freshly-prepared hydrazine compounds. However, following preincubation in medium for 6--12 h, isoniazid alone at high concentrations (10(-2) M--10(-1) M) induced DNA repair. With isoniazid/manganese mixtures, preincubation did not further enhance DNA repair except at low concentrations of isoniazid (2--5 x 10(-4) M). Catalase reduced the DNA damage caused by preincubated isoniazid and by the isoniazid/metal mixtures. Exposure of repair-deficient xeroderma pigmentosum cells to isoniazid plus manganese resulted in a DNA-repair profile similar to that of normal cells. The results are consistent with hydrogen peroxide being a critical intermediate for the production of free radicals which cause the observed DNA damage.
 ...
PMID:Enhancement by transition metals of unscheduled DNA synthesis induced by isoniazid and related hydrazines in cultured normal and xeroderma pigmentosum human cells. 51 96

Several data suggest a relationship of poly(ADP-ribose) (PAR) synthesis to DNA repair and the influence of some trace elements on the semiconservative and unscheduled DNA synthesis (UDS). Previously we found certain alterations in the UV-light induced UDS and in the contents of trace elements in the lymphocytes of patients with light sensitive skin disorders. In the recent study in polymorphic light eruption, cutaneous porphyrias and xeroderma pigmentosum the PAR synthesis and zinc, copper and manganese contents in the chromatin of the lymphocytes (measured by neutron activation analysis) were investigated. UV induced PAR synthesis was generally lower in the cells of polymorphic light eruption and especially in xeroderma pigmentosum with a reduced repair capacity whereas in cutaneous porphyrias no difference was observed. Some correlations occurred between the contents of trace elements studied and UDS as well in each group tested. It seems that PAR investigations throw new light upon our understanding of the pathomechanism of photodermatoses.
 ...
PMID:Poly(ADP-ribose)-synthesis and excision repair in light sensitive skin disorders. 209 34