Reoxygenation in quiescent and total intratumor cells following thermal neutron irradiation with or without (10)B-compound-compared with that after gamma-ray irradiation.
OBJECTIVE
Reoxygenation in quiescent (Q) and total tumor cells within solid tumors after thermal neutron irradiation with or without (10)B-compound was examined, comparing with that following gamma-ray irradiation.


METHODS
C3H/He mice bearing SCC VII tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-(10)B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-(10)B (BPA), the tumors were irradiated with thermal neutrons, or those without (10)B-compounds were irradiated with thermal neutrons alone or gamma-rays. At various time points after each treatment, a series of test doses of gamma-rays were given to tumor-bearing mice while alive or after being killed to obtain hypoxic fractions in the tumors. Immediately after irradiation, the tumors were excised, minced, and trypsinized. Following incubation of tumor cells with cytokinesis blocker, the micronucleus (MN) frequency in cells without BrdU labeling ( = Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU. The MN frequency of BrdU-unlabeled cells was then used to calculate the surviving fraction of the unlabeled cells from the regression line for the relationship between the MN frequency and the surviving fraction of total tumor cells.


RESULTS
In both total and Q tumor cells, the hypoxic fractions immediately after each treatment went up suddenly. Reoxygenation after each treatment occurred more rapidly in total cells than in Q cells. In both cell populations, reoxygenation appeared to be rapidly induced in the following order: neutron irradiation without (10) gamma-ray irradiation.


CONCLUSIONS
Based on our previous report that total and Q cell fractions within these tumors have larger acutely and chronically hypoxic fractions, respectively, acute hypoxic cells appeared to play a larger role in reoxygenation. BSH was thought to have a potential to distribute more homogeneously in solid tumors than BPA, because BSH induced the nearer reoxygenation pattern to that following neutron irradiation alone than BPA.
Masunaga
S
S
Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, Noda, Sennan-gun, Osaka, Japan.
Ono
K
K
Suzuki
M
M
Sakurai
Y
Y
Kobayashi
T
T
Takagaki
M
M
Kinashi
Y
Y
Akaboshi
M
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic; D001895:Boron / Q000032:analysis; D016754:Boron Neutron Capture Therapy; D001973:Bromodeoxyuridine; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000503:physiopathology* / Q000532:radiotherapy*; D002455:Cell Division / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology*; D002470:Cell Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007554:Isotopes / Q000032:analysis; D018499:Linear Energy Transfer; D051379:Mice; D008809:Mice, Inbred C3H; D015162:Micronucleus Tests / Q000379:methods; D010101:Oxygen Consumption / Q000502:physiology*; D011838:Radiation-Sensitizing Agents; D011853:Radiobiology; D012044:Regression Analysis
D000964:Antimetabolites, Antineoplastic; D007554:Isotopes; D011838:Radiation-Sensitizing Agents; D001973:Bromodeoxyuridine; D001895:Boron