Effects of Cell Cycle Position on Ionizing Radiation Mutagenesis. I. Quantitative Assays of Two Genetic Loci in a Human Lymphoblastoid Cell Line

Abstract

Relatively little work has been done on the influence of the position of the cell in the cell cycle on ionizing radiation-induced mutagenesis. We synchronized WTK1 human lymphoblastoid cells with 200 microM lovastatin for 48 h; under these conditions more than 80% of the cells were arrested in G1 phase. Upon release, there was a 12-15-h lag followed by movement of a large fraction into S phase. We irradiated cells with 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 G1 and into S phase, and more resistant in mid to late S and G2/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 G1 through mid-S phase were most sensitive to radiation-induced mutations at the autosomal thymidine kinase (TK) locus, whereas G1 phase was the most sensitive phase at the X-linked hypoxanthine guanine phosphoribosyl transferase (HPRT) locus.

Tracking Chemical Changes in a Live Cell: Biomedical Applications of SR‐FTIR Spectromicroscopy

“…The normal human fetal lung fibroblast IMR-90 P4 (passage 4) cell line of female origin was used for this study [58]. Grown to confluency, the cells are ∼82% synchronized into the G 1 phase as determined by fluorescence-activated cell sorting (FACS) [18,20,21].…”

Modeling Dose Deposition and DNA Damage Due to Low-Energy β–Emitters

“…The published literature suggests that such cell cycle variation is rather modest and that cellular radiosensitivity is not consistently greatest in G 2 /M. For mutation induction at the Tk locus, human lymphblastoid cell lines were most radiosensitive in late G 1 to mid-S phase; for HPRT locus mutation, G 1 phase was most radiosensitive (Chuang and Liber, 1996). In mouse L cells, G 1 and G 2 /M phases were most sensitive to mutation induction at the HPRT locus in one study (Evans et al, 1996); in a second study G 2 /M was more specifically sensitive to neutrons but not to gamma rays (Tauchi et al, 1993).…”

“…Accordingly the same majority of Committee members also considered that mutational radiosensitivity in the G 2 phase of the cell cycle is usually enhanced by less than a factor of ten (eg Al-Achkar et al, 1988;Redpath and Sun, 1990;Chuang and Liber, 1996;Evans et al, 1996).…”