Hyperthermia and incorporation of halogenated pyrimidines: radiosensitization in cultured rodent and human tumor cells.
OBJECTIVE
To investigate the possible benefit of hyperthermia (HT) in combination with radiosensitization by halogenated pyrimidines (HPs) in rodent as well as in human tumor cells.


METHODS
Exponentially growing rodent cells, radiosensitive R-1 and MOS cells and radioresistant RUC-II and V79 cells, and human SW1573 cells, were exposed to 0, 1, 2, and 4 microM of chloro- (CldUrd), bromo- (BrdUrd), or iodo-deoxyuridine (IdUrd) in the culture medium. Survival after irradiation with gamma-rays from a 137Cs source and/or hyperthermic treatment (HT, 60 min at 42 degrees C) was determined by clonogenic assay. Linear-quadratic analyses of the radiation survival curves were performed to assess sensitization in the dose range 1 to 3 Gy relevant to radiotherapy.


RESULTS
The incorporation of HPs sensitized all cell lines to HT and resulted in radiosensitization dependent on the percentage of thymidine replacement. At equal levels of thymidine replacement, IdUrd was the most potent radiosensitizer. HT further increased radiation-induced lethality of cells that had incorporated HPs. Linear-quadratic analyses showed that HT further increased the linear parameter of the LQ formula while the quadratic parameter was not significantly changed.


CONCLUSIONS
The combination of HT and HPs act additively in increasing the radiosensitivity of rodent tumor cell lines with varying radiosensitivities as well as of a human tumor cell line. In particular, the ratio of the linear parameter to the quadratic parameter, relevant for fractionation effects in radiotherapy, was increased.
Van Bree
C
C
Academic Medical Center, University of Amsterdam, Department of Radiotherapy, The Netherlands.
Franken
N A
NA
Bakker
P J
PJ
Klomp-Tukker
L J
LJ
Barendsen
G W
GW
Kipp
J B
JB
D000818:Animals; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D002470:Cell Survival / Q000528:radiation effects; D003131:Combined Modality Therapy; D006224:Cricetinae; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006979:Hyperthermia, Induced; D007065:Idoxuridine / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects
D011838:Radiation-Sensitizing Agents; D001973:Bromodeoxyuridine; D007065:Idoxuridine; D003857:Deoxyuridine