Persistence of chromatid damage after G2 phase X-irradiation in lymphoblastoid cells from Gardner's syndrome

Abstract

Previous reports showed that skin fibroblasts or peripheral blood lymphocytes from individuals with hereditary cancer or with a genetic disorder predisposing to cancer show an abnormally high frequency of chromatid damage after X-irradiation in G2 phase. The reproducibility of this response suggested that it could provide the basis of an assay for genetic predisposition to cancer. The present blind study tested whether lymphoblastoid cell lines could also be used in this assay. Lymphoblastoid cell lines from patients with Gardner's syndrome (GS) were compared with those from clinically normal controls. In metaphase cells collected during the first 30 min after X-irradiation (58R), frequencies of chromatid breaks and gaps were similar in GS and normal cells. However, in metaphase cells collected from 0.5 to 1.5 h and 1.5 to 2.5 h after X-irradiation, the total unrepaired damage for each GS cell line was greater than that observed in any of the lines from clinically normal controls. The persistence of chromatid damage in the GS cells after X-irradiation suggests a deficiency or imbalance in the repair or processing of the radiation-induced DNA damage. The results show that lymphoblastoid cell lines in early passage can be used in this cytogenetic assay to identify members in a GS family who have the GS gene(s) or other individuals with a genetic predisposition to cancer.