Interaction between the microtubule inhibitor tubulozole and gamma-irradiation in murine tumors in vivo.
The combined effect of the microtubule inhibitor tubulozole and gamma-irradiation has been investigated in vivo in subcutaneous MO4 fibrosarcomas and Lewis Lung carcinomas. A marked interactive effect on tumor growth was observed when 160 mg/kg tubulozole was orally administered before the tumors were treated with 10 Gy radiation. Dose dependency and optimal effect were obtained on tumor growth of MO4 tumor bearing animals when the drug treatment was given 6 hr prior to the irradiation. The optimal pretreatment time coincided with the time at which a peak mitotic index in the tumor tissue was observed. An enhancing effect is also noticed at other doses of radiation in MO4 tumors pretreated 6 hr before with 160 mg/kg tubulozole. The interactive effect is maintained in a clinically relevant dose fractionation schedule whereby 8 fractions of 2 Gy each were pretreated 6 hr before with 80 mg/kg tubulozole. Tubulozole-T, the stereo-isomer of tubulozole, neither exhibits any antimicrotubular action nor exerts an antitumoral effect on its own or in combination with gamma-irradiation. The possible mechanisms of interaction between tubulozole and gamma-irradiation in tumor tissue are discussed.
Distelmans
W
W
Department of Life Sciences, Janssen Research Foundation, Beerse, Belgium.
Van Ginckel
R
R
Vanherck
W
W
Willebrords
R
R
De Brabander
M
M
Wouters
L
L
Van den Winkel
P
P
De Backer
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002460:Cell Line; D003037:Cobalt Radioisotopes; D003131:Combined Modality Therapy; D004148:Dioxolanes / Q000627:therapeutic use*; D004149:Dioxoles / Q000627:therapeutic use*; D005354:Fibrosarcoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D005720:Gamma Rays; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation
D000970:Antineoplastic Agents; D003037:Cobalt Radioisotopes; D004148:Dioxolanes; D004149:Dioxoles; C040422:tubulazole