Are hypoxic cells critical for the outcome of fractionated radiotherapy in a slow-growing mouse tumor?
OBJECTIVE
To investigate the significance of hypoxic cells, reoxygenation and repopulation for the outcome of fractionated radiotherapy of a slow-growing subline of a murine fibrosarcoma and to compare the results with those previously obtained from the original fast-growing tumor.


METHODS
A slow-growing subline, 457-O, was obtained among the tumors that recurred after a single irradiation to the third generation isotransplants of a mouse fibrosarcoma, FSa-II. The single cell suspensions were transplanted into the mouse foot and when the tumors reached an average diameter of 4 mm, they were subjected to one to 20 equal daily y-ray doses given in air (A) or under hypoxic conditions (H). The TCD50 (50% tumor control radiation dose) was calculated according to the tumor control frequency within 180 days. The linear-quadratic plus time model was fitted to these data by logistic regression analysis.


RESULTS
The volume doubling time of the 457-O tumors was approximately 2.2 times slower than that of the original FSa-II tumors. The TCD50(H) (single dose) was 52.3 Gy and increased with an increasing number of fractions to a TCD50(H) (20 doses) of 90.8 Gy. This increase of 38.5 Gy was much smaller than that of 149 Gy for the original FSa-II. The TCD50(A) (single dose) and TCD50(A) (20 doses) were 41.3 and 50.6 Gy, respectively. This small difference of 9.3 Gy contrasted with a significant increase of 52.9 Gy for the FSa-II.


CONCLUSIONS
These results suggested no repopulation of 457-O tumor clonogens during the course of up to 20 daily doses, while the original FSa-II tumor cells repopulated substantially. Hypoxic clonogens in the slow-growing tumor reoxygenated but some fractions remained critical.


CONCLUSIONS
The present data together with those obtained from the fast-growing FSa-II suggested that hypoxic clonogens were critical for the outcome of fractionated radiotherapy. Repopulation was insignificant in this slow-growing tumor during five to 20 daily doses.
Urano
M
M
Department of Radiation Medicine, University of Kentucky Medical Center, Lexington 40536-0084, USA.
Nishimura
Y
Y
Kuroda
M
M
Reynolds
R
R
D000818:Animals; D002455:Cell Division / Q000528:radiation effects; D015687:Cell Hypoxia / Q000502:physiology / Q000528:radiation effects; D002999:Clone Cells / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005354:Fibrosarcoma / Q000473:pathology / Q000532:radiotherapy*; D005534:Foot Diseases / Q000532:radiotherapy; D005720:Gamma Rays / Q000627:therapeutic use; D016014:Linear Models; D016015:Logistic Models; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D010101:Oxygen Consumption / Q000528:radiation effects; D011879:Radiotherapy Dosage; D016896:Treatment Outcome