The intrinsic alpha/beta ratio for human tumour cells: is it a constant?
The radiation response of 15 mammalian cell lines comprising 11 human tumour, two human fibroblast and two murine lymphoma cell lines, has been analysed using the linear-quadratic equation. As well as using conventional analysis of acute dose-survival curves to derive values for alpha and beta (termed alpha ac and beta ac), low dose-rate and split-dose experiments have been used to derive independent values of alpha and beta (alpha 1dr and beta RR), respectively. alpha 1dr provides a measure of irrecoverable damage, the magnitude of which agreed well with the initial slope of the acute survival curve for most cell lines. beta RR derived from split-dose experiments represents a unique measure of recovery for each cell line. Large differences were found between individual values of beta ac and beta RR, especially in the radiosensitive cell lines. Since beta RR is a functional measure of recovery we suggest that this is the more relevant parameter in studies of dose sparing. The most striking result of this analysis was found in considering the alpha/beta ratios. No relationship was observed between alpha ac and beta ac resulting in values of alpha ac/beta ac ranging from 1 to 175. In contrast a positive correlation was observed between alpha 1dr beta RR in the 11 tumour cell lines, giving an alpha/beta ratio of 9.4 +/- 1.8 Gy. This observation of the relative constancy of the ratio for human tumour cells leads to an hypothesis about the role of initial damage as a determinant of radiosensitivity.
Radiotherapy Research Unit, Institute of Cancer Research, Sutton, Surrey, UK.
J H
JH
Peacock
J J
JJ
Eady
S M
SM
Edwards
T J
TJ
McMillan
G G
GG
Steel
D000818:Animals; D002470:Cell Survival / Q000528:radiation effects*; D003037:Cobalt Radioisotopes; D004249:DNA Damage / Q000502:physiology; D004273:DNA, Neoplasm / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D051379:Mice; D011836:Radiation Tolerance / Q000502:physiology*; D014407:Tumor Cells, Cultured
D003037:Cobalt Radioisotopes; D004273:DNA, Neoplasm