Sensitivity to ultraviolet radiation in a dominantly inherited form of xeroderma pigmentosum.

An Australian family is described in which a mild form of xeroderma pigmentosum (XP) is inherited as an autosomal dominant trait. Studies of lymphoblastoid cells and fibroblasts from affected persons demonstrated cellular sensitivity to ultraviolet (UV) light as judged by diminished clonogenicity and higher frequencies of UV induced chromosome aberrations compared to normal controls. After UV irradiation of dominant XP cells, replicative DNA synthesis was depressed to a greater extent than normal and the level of UV induced DNA repair synthesis was lower than that in normal cells.

Effect of caffeine on gamma-ray-induced G2 delay in ataxia telangiectasia.

Exposure of normal control and ataxia-telangiectasia (A-T) lymphoblastoid cell lines to ionizing radiation gives rise to an increase in the proportion of G2 phase cells. The size and extent of the G2 phase block is greater in A-T cells than in normal cells. Caffeine has a similar overall effect in control and A-T cell lines in reducing the G2 arrest observed after ionizing radiation.

Gene dosage and complementation analysis of ataxia telangiectasia lymphoblastoid cell lines assayed by induced chromosome aberrations.

An approach of general applicability to mammalian radiosensitive mutants has been used in the analysis of gene dosage and complementation in ataxia telangiectasia (A-T). Thymidine residues in DNA of one parental lymphoblastoid cell line were substituted with bromodeoxyuridine before fusion with a second parental cell line, to allow differential staining of the two sets of chromosomes. Following gamma-irradiation, induced chromosome aberrations were scored in diploid and homokaryon cells from each parental line as well as in heterokaryons.

Wilms' tumour: association with cellular sensitivity to mitomycin C in patients and first-degree relatives.

To investigate whether predisposition to Wilms' tumour is associated with a particular defect in the handling of DNA damage, cell-lines from families in which the tumour had occurred were tested for sensitivity to a variety of DNA-damaging agents. Lymphoblastoid lines from both Wilms' tumour patients and their first-degree relatives showed increased sensitivity to the cross-linking agent, mitomycin C, but normal sensitivity to ultraviolet (UV) and gamma irradiation. Thus sensitivity to mitomycin C damage can be associated with the Wilms'-tumour-susceptible genotype and could be a genetic factor responsible for the modification of expression of this genotype.