Familial keratoses of actinic distribution associated with internal malignancy and cellular hypersensitivity to UVA.

In members of a family there appeared to be an association between the development of cutaneous pigmented keratoses in sun-exposed sites, and the later evolution of internal malignancies, particularly carcinoma of the uterus. Affected individuals were not clinically photosensitive, but their fibroblasts demonstrated gross cytopathic changes, low survival indices and an increased frequency of DNA single strand breaks following exposure to long-wave ultraviolet radiation (UVA). These clinical and cellular features appear to identify an unrecognized syndrome that may not be uncommon.

PRUFILE: a clinical and laboratory database for the genetics centre.

The growing complexity and volume of workload in a Clinical Genetics Centre can rapidly swamp the available clerical facilities. The multiuser database described gives facilities not only for administrative control and documentation but also for the production of data for clinical and scientific analysis. The close link between clinical and laboratory databases gives great versatility and easy expansion as new tests and disciplines are applied to clinical genetic problems.

Cellular hypersensitivity to UV-A: a clue to the aetiology of actinic reticuloid?

Fibroblasts cultured from six patients with actinic reticuloid (AR) showed striking cytopathic changes and inhibition of RNA synthesis after exposure to near-ultraviolet radiation that had no effect on normal and other photosensitive cell strains, such as those of xeroderma pigmentosum and Bloom syndrome. An abnormal pattern of DNA fragmentation was observed after doses insufficient to cause cytopathic effects. These results suggest a cellular defect in the prevention or repair of some damage caused by free radicals and other photoproducts.

The effect of aphidicolin on the rate of DNA replication and unscheduled DNA synthesis of Bloom syndrome and normal fibroblasts.

Ultraviolet radiation induced more unscheduled DNA synthesis (UDS) in ten Bloom syndrome (BS) fibroblast strains than in control cells, but this difference could be suppressed by aphidicolin treatment in at least nine BS strains. Aphidicolin, 1 and 5 micrograms/ml, were required to inhibit by 30% the UDS of BS and control cells respectively, but the DNA replication of BS cells did not prove abnormally sensitive to such an inhibitor. These findings are discussed in relation to current knowledge of the action of aphidicolin and hypotheses of the metabolic defect in BS.

Tendency to high levels of UVR-induced unscheduled DNA synthesis in Bloom syndrome.

The unscheduled DNA synthesis (UDS) induced by ultraviolet radiations (UVR) in fibroblasts from 5 patients with Bloom Syndrome (BS) has been studied. Since often a high proportion of BS cells has large, probably polyploid nuclei, care was taken to select cells of normal size. Furthermore, UDS was usually measured over constant nuclear areas by a photometric method and each cell strain was tested on several different occasions.