Radiation-induced cell cycle delay measured in two mouse tumors in vivo using bromodeoxyuridine.
The magnitude of the delay of cells in the phases of the cell cycle after irradiation may be related to the radioresponsiveness of tumor cell populations. In this study we have quantified division delay in two mouse tumors in vivo after single and fractionated doses of X rays and single doses of neutrons. The incorporation of bromodeoxyuridine and flow cytometry provided a sensitive and quantitative method to detect cell cycle perturbations after radiation treatment. The more rapidly growing SAF tumor showed less G2-phase delay per gray than a more slowly proliferating tumor, the Rh (0.9 vs 1.8 h). In addition, the SAF tumor failed to show any G1/S-phase delay while the Rh tumor experienced a longer G1-phase delay than that measured for G2 phase (3.1 vs 1.8 h). There was a trend in both tumors for lower doses to be more effective in producing cell cycle delays. Neutrons caused longer G2-phase delays on a unit dose basis, 2.5 and 5.4 h for the SAF and Rh tumors, respectively. The RBE for neutrons for division delay was found to be 2.9 and 2.8 for the SAF and Rh tumors, while the RBE for growth delay was 3.4 and 3.5. Fractionation of the X-ray dose caused a reduction in division delay at higher total doses (10 or 12 Gy) but was without effect at the lower dose studied (6 Gy). These studies show the feasibility of measuring cell cycle delays in vivo, and future developments are suggested for a possible predictive test in patients receiving radiotherapy.
Wilson
G D
GD
CRC Gray Laboratory, Mount Vernon Hospital, Northwood, Middlesex, England.
Martindale
C A
CA
Soranson
J A
JA
Bourhis
J
J
Carl
U M
UM
McNally
N J
NJ
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism*; D002453:Cell Cycle / Q000528:radiation effects*; D002455:Cell Division / Q000528:radiation effects; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011829:Radiation Dosage; D012062:Relative Biological Effectiveness; D012513:Sarcoma, Experimental / Q000473:pathology
D001973:Bromodeoxyuridine