Chromosomal sensitivity to X-ray irradiation during the G(2) phase in lymphocytes of patients with hereditary cutaneous malignant melanoma as compared to healthy controls

Recent reports have suggested that elevated chromosomal aberration yields f ollowing X-ray irradiation of skin fibroblasts and peripheral lymphocytes i n the G(2) phase of the cell cycle are characteristic of affected members o f cancer-prone families. These studies propose that the phenomenon is a con sequence of impaired caffeine- and arabinofuranosylcytosine (ara-C)sensitiv e DNA repair and might be a useful indicator of genetic susceptibility to c ancer. We have tested G(2) chromosomal X-ray sensitivity in peripheral bloo d lymphocytes from members of kindreds with hereditary cutaneous malignant melanoma (HCMM) combined with the dysplastic nevus syndrome (DNS), disorder s in which susceptibility to skin cancer is inherited in an autosomal domin ant pattern. In the assay lymphocytes from patients with HCMM/DNS exhibited responses indistinguishable from normal healthy controls. Furthermore, the radiation-induced aberration yields were potentiated to the same strong ex tent by post-treatments with caffeine, or a combination of ara-C and hydrox yurea, both in lymphocytes from individuals with HCMM/DNS and lymphocytes f rom healthy controls. Thus, lymphocytes of affected patients with HCMM/DNS do not have an increased sensitivity to X-ray irradiation in the G(2) phase of the cell cycle. (C) 1999 Elsevier Science B.V. All rights reserved.