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Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have assessed the role of cellular transformation in ultraviolet (uv)-induced mutagenic events in human cells. To maintain uniformity of genetic background and to eliminate the effect of DNA repair, primary nontransformed lymphocytes (T-cells) and Epstein-Barr virus-transformed lymphocytes (B-cells) from one patient (XP12Be) with the DNA repair-deficient disorder xeroderma pigmentosum (group A) were transfected with the mutagenesis shuttle vector pZ189. Parallel control experiments were performed with primary, nontransformed lymphocytes from a normal individual and with a repair-proficient Epstein-Barr virus-transformed lymphocyte line (KR6058). pZ189 was treated with uv and introduced into the four cell lines by electroporation. Plasmid survival and mutations inactivating the marker supF suppressor tRNA gene in the recovered pZ189 were scored by transforming an indicator strain of Escherichia coli. Plasmid survival was reduced and mutation frequency elevated equally with both XP-A cell lines compared to both normal cell lines. Base sequence analysis of more than 250 independent plasmids showed that while the G:C----A:T base substitution mutation was found in at least 60% of plasmids with single or tandem mutations with all four cell lines, the frequency with the transformed XP-A (93%) cells was significantly higher (P less than 0.01) than that with the nontransformed XP-A cells (77%). In addition, with the transformed XP-A cells, there were significantly fewer plasmids with transversions and with mutations at a transversion hotspot (base pair 134) than with plasmids recovered from nontransformed XP-A cells. Interleukin-2 and phytohemagglutinin (used to maintain growth of the nontransformed lymphocytes) treatment of transformed XP12Be cells did not change overall plasmid survival or mutation frequency, but increased the transversion frequency and induced a mutational hotspot (at base pair 159), while another mutational hotspot (at base pair 123) disappeared. Thus we have demonstrated that in repair-deficient human cells, cellular transformation, while not affecting overall postuv plasmid survival and mutation frequency, does increase the susceptibility to G:C----A:T transition mutations, a type of mutation associated with uv-induced neoplasia.
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PMID:Ultraviolet mutagenesis in human lymphocytes: the effect of cellular transformation. 132 18

gamma-Ray and UV sensitivities of phytohemagglutinin (PHA)-stimulated T-lymphocytes were examined in the presence of the recombinant human interleukin-2 (IL-2). D0 values for the survival curves after gamma-irradiation varied from 0.90 to 1.25 Gy, and were comparable to those reported for human fibroblast cells. By fractionated exposure of gamma-rays, T-lymphocytes were shown to have the repair capacity for the sublethal damage. UV-survival curves yielded D0 of 6.5 J/m2 for T-lymphocytes from normal donors. T-Lymphocytes from a xeroderma pigmentosum patient with extremely low excision repair were markedly hypersensitive to UV (D0, 1.4 J/m2). T-Lymphocytes may be used to detect individuals who are sensitive to radiation or chemicals, and this method takes less time than that using fibroblast cells.
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PMID:Radiation sensitivity of T-lymphocytes grown with recombinant human interleukin-2. 349 97