S. Masunaga et al., ALTERATION OF RADIOSENSITIVITY OF QUIESCENT CELL-POPULATIONS IN SOLIDTUMORS IRRADIATED WITH X-RAYS TWICE AT VARIOUS INTERVALS, Japanese journal of cancer research, 84(11), 1993, pp. 1130-1135
5-Bromo-2'-deoxyuridine (BUdR) was injected into SCC VII or EMT6/KU tu
mor-bearing mice intraperitoneally to label all the proliferating tumo
r cells. First, the mice were irradiated with X-rays at a dose of 10 G
y, followed by a dose of 0-20 Gy at 0, 12, 24 or 48 h later. During th
e interval, no BUdR was injected. Immediately after the second irradia
tion, the tumors were excised and trypsinized. The micronucleus (MN) f
requency in cells without BUdR labeling was determined by means of inc
ubation with cytochalasin-B (a cytokinesis-blocker) and immunofluoresc
ence staining for BUdR. When the tumors were not pretreated with BUdR
before the first irradiation, the MN frequency in all tumor cells was
determined. To determine the labeling indices of SCC VII and EMT6/KU t
umors at the time of the second irradiation, each group also included
mice that were continuously administered BUdR until just before the se
cond irradiation using mini-osmotic pumps which had been implanted sub
cutaneously 5 days before the first irradiation. The MN frequency of a
ll tumor cell populations obtained immediately after the second irradi
ation decreased in proportion to the increase in interval time. Howeve
r, in both tumor systems, the MN frequency of unlabeled cell populatio
ns, which could be regarded as quiescent cells in the tumors at the ti
me of the first irradiation, was raised with increase in the interval
time. In addition, the labeling index at the second irradiation was hi
gher than that at the first irradiation. These findings support the oc
currence of recruitment from quiescent to proliferating state during f
ractionated irradiation.