ABSENCE OF EXCISION OF ULTRAVIOLET‐INDUCED CYCLOBUTANE DIMERS IN XERODERMA PIGMENTOSUM *

XERODERMA pigmentosum is a rare human skin disease which is inherited as an autosomal recessive mutation and has been known by dermatologists for nearly a century [ 1-31. The major clinical symptom is high actinic skin carcinogenesis [ 1.4.51. There are two forms of the disease: one shows only the skin symptoms, the other more uncommon form shows additional neurological symptoms and is known as the de Sanctis Cacchione syndrome [5-71. Whether the neurological symptoms should be regarded as part of xeroderma pigmentosum or due to separate genetic factors is as yet unknown [2,5-71. Fibroblasts[& 91 and epithelial cells[lO] from the skin in both forms of this disease appear to perform low or negligible amounts of DNA repair replication after irradiation with ultraviolet (u.v.) light, but the level of such residual amounts cannot yet be correlated with the two forms of the disease since the number of cases studied thus far is too small[& 111. Previous studies on DNA repair in de Sanctis Cacchione skin fibroblasts suggested that an early step in DNA repair involving enzymatic strand breakage is defective [9,12]. Such an hypothesis has also been advanced by Setlow et al. [ 131 for skin fibroblasts from the non-neurological form of xeroderma pigmentosum. They showed that thymine-containing dimers are excised after U.V. damage of normals cells but not of xeroderma cells. Since the two forms of the disease might show some biochemical differences, we have now investigated the excision of thyminecontaining dimers in cultured cells from patients with the de Sanctis Cacchione syndrome. Preliminary results of this investigation have already been reported [9, 121. Sterile 1 mm punch biopsies were taken from apparently normal regions of the arms of three de Sanctis Cacchione patients and two normal persons. Fibroblast cultures were developed in Eagle's minimum essential medium with 3 mglml dextrose, non-essential amino acids, and 15 percent fetal calf serum. Usually, 1-5-2 months elapsed between the time of biopsy and the start of any experiments with fibroblast cultures. They were then used throughout the period of steady growth until cultures degenerated[ 14, IS]. Human embryonic fibroblasts (WI-38) were also used and these