TY - JOUR

T1 - Hprt mutation spectrum in a closely related pair of human bladder tumour cell lines after gamma-irradiation at different dose-rates.

AU - Edwards, S. M.

AU - Kent, C. R. H.

AU - McMillan, T. J.

PY - 1997/2

Y1 - 1997/2

N2 - The spectrum of deletion sizes in mutants of two human bladder carcinoma cell lines has been examined. The cell lines were MGH-U1 and a radiation-sensitive subline (U1-S40b) that has been developed in this laboratory. Three groups, each of 20-30 mutants at the hprt locus were investigated: arising spontaneously, or induced after exposure to 10 Gy gamma radiation either at high dose-rate (2 Gy/min) or low dose-rate (0.01 Gy/min). Data on the mutation frequency of the two cell lines at low dose-rate were obtained to supplement previously published data at high dose-rate. The mutation frequency was lower in U1-S40b than in MGH-U1 both for high and low dose-rate irradiation. The presence of intact copies of each of the nine hprt exons was examined using multiplex PCR, supplemented by single-exon PCR. The incidence of small hprt mutations (i.e. leading to no change in the size of the PCR products) was the same for spontaneous mutations in the two cell lines; for radiation-induced mutants it was higher in U1-S40b. The incidence of total deletions (i.e. no positive exon amplification) was lower in U1-S40b both for high and low dose-rate irradiation. The results are consistent with the hypothesis that large deletions tend to lead to the loss of adjacent essential genes and thereby to the death of potential mutants.

AB - The spectrum of deletion sizes in mutants of two human bladder carcinoma cell lines has been examined. The cell lines were MGH-U1 and a radiation-sensitive subline (U1-S40b) that has been developed in this laboratory. Three groups, each of 20-30 mutants at the hprt locus were investigated: arising spontaneously, or induced after exposure to 10 Gy gamma radiation either at high dose-rate (2 Gy/min) or low dose-rate (0.01 Gy/min). Data on the mutation frequency of the two cell lines at low dose-rate were obtained to supplement previously published data at high dose-rate. The mutation frequency was lower in U1-S40b than in MGH-U1 both for high and low dose-rate irradiation. The presence of intact copies of each of the nine hprt exons was examined using multiplex PCR, supplemented by single-exon PCR. The incidence of small hprt mutations (i.e. leading to no change in the size of the PCR products) was the same for spontaneous mutations in the two cell lines; for radiation-induced mutants it was higher in U1-S40b. The incidence of total deletions (i.e. no positive exon amplification) was lower in U1-S40b both for high and low dose-rate irradiation. The results are consistent with the hypothesis that large deletions tend to lead to the loss of adjacent essential genes and thereby to the death of potential mutants.

U2 - 10.1080/095530097144292

DO - 10.1080/095530097144292

M3 - Journal article

VL - 71

SP - 177

EP - 184

JO - International Journal of Radiation Biology

JF - International Journal of Radiation Biology

SN - 0955-3002

IS - 2

ER -