EFFECTS OF CELL-CYCLE POSITION ON IONIZING-RADIATION MUTAGENESIS .1. QUANTITATIVE ASSAYS OF 2 GENETIC-LOCI IN A HUMAN LYMPHOBLASTOID CELL-LINE

Relatively little work has been done on the influence of the position of the cell in the cell cycle on ionizing radiation-induced mutagenesi s. We synchronized WTK1 human lymphoblastoid cells with 200 mu M lovas tatin for 48 h; under these conditions more than 80% of the cells were arrested in G(1) phase. Upon release, there was a 12-15-h lag followe d by movement of a large fraction into S phase. We irradiated cells wi th either 1.5 Gy X rays at 1, 15, 18, 21 or 24 h or 1.5 Gy gamma rays at 1, 5, 10, 15 or 24 h after release from lovastatin. We showed that WTK1 cells were most sensitive to ionizing radiation-induced toxicity in G(1) and into S phase, and more resistant in mid to late S and G(2) /M phase. Somewhat surprisingly, we found that the two different gene loci had different sensitivities to radiation-induced mutation through the cell cycle. Cells in late G(1) through mid-S phase were most sens itive to radiation-induced mutations at the autosomal thymidine kinase (TK) locus, whereas G(1) phase was the most sensitive phase at the X- linked hypoxanthine guanine phosphoribosyl transferase (HPRT) locus. ( C) 1996 by Radiation Research Society