Cell-cycle progression during continuous low dose rate irradiation of a human bladder carcinoma cell line.
At very low radiation dose rates, the proliferation of mammalian cells continues unaffected but as the dose rate is increased there comes a point at which it is interrupted. The dose rate at which this happens is often thought to be a significant factor in the effects of brachytherapy: it may determine the range from an implanted source at which cell-cycle redistribution and repopulation effects will occur. By means of mitotic counts and DNA flow cytometry, we have examined the dose rate effect in a human bladder carcinoma cell line (MGH-U1). Irradiation at dose rate 0.1 cGy/min had little or no effect on cell-cycle progression. Suppression of mitosis and arrest of cells in G2 was observed at 0.4 cGy/min and above. Surprisingly, the duration of mitotic arrest showed little dose rate dependence; it was followed by an overshoot of cells in mitosis after 24-39 h of irradiation. An even more pronounced overshoot of cells in G2 occurred and persisted throughout the irradiation period. The cell kinetic data indicate that after the temporary block in cell-cycle progression, cell proliferation continued at all dose rates up to 1.4 cGy/min. We have evaluated these results in the light of previous studies in this department of the dose rate effect for cell survival in the MGH-U1 cell line. After 24 h irradiation at 1.4 cGy/min the surviving fraction was below 10(-2), also after 30 h at 1.0 cGy/min. When cell-cycle blockade is considerable, so is the level of cell killing. Flow-cytometric data therefore are dominated by the properties of cells that are doomed to die.(ABSTRACT TRUNCATED AT 250 WORDS)
Skladowski
K
K
Centre of Oncology, Maria Sklodowska-Curie Memorial Institute, Wybrzeze Armii Czerwonej, Poland.
McMillan
T J
TJ
Peacock
J
J
Titley
J
J
Steel
G G
GG
D002453:Cell Cycle; D004273:DNA, Neoplasm / Q000032:analysis; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D006801:Humans; D008940:Mitotic Index; D011879:Radiotherapy Dosage; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*
D004273:DNA, Neoplasm