Study of arsenic trioxide-induced vascular shutdown and enhancement with radiation in solid tumor.
OBJECTIVE
Arsenic trioxide (ATO) has been reported to be an effective chemotherapeutic agent for acute promyelocytic leukemia (APL), and, recently, anti-tumor effect has been demonstrated in solid tumors. However, little is known about the mechanism of action of the ATO effect on solid tumor. We investigated the anti-vascular effect of ATO and the potential of combining ATO with radiation therapy.


METHODS
We studied the anti-vascular effect of ATO and radiosensitization of squamous cell carcinoma (SCC) VII murine tumors of C3H mice. The anti-vascular effect was examined using magnetic resonance imaging(MRI), and radiosensitivity was studied by clonogenic assay and tumor growth delay. Histopathological changes of the tumors after various treatments were also observed with hematoxylin and eosin (H&E) staining.


RESULTS
Necrosis and blood flow changes in the central region of tumors in the hind limbs of the animals were observed on T2-weighted imaging after an i.p. injection of 8 mg/kg of ATO alone. ATO exposure followed by radiation decreased the clonogenic survival of SCC VII cells compared with either treatment alone. Tumor growth delay after 10-20 Gy of radiation alone was increased slightly compared with control tumors, but the combination of ATO injection 2 hours before exposure to 20 Gy of radiation significantly prolonged tumor growth delay by almost 20 days.


CONCLUSIONS
The results suggest that ATO and radiation can enhance the radiosensitivity of solid tumor.
Department of Radiology, Otsu Red Cross Hospital, 1-35 Nagara, Otsu-shi, Shiga 520-8511, Japan.
Hajime
H
Monzen
Robert J
RJ
Griffin
Brent W
BW
Williams
Morikazu
M
Amano
Satoshi
S
Ando
Takeo
T
Hasegawa
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D001808:Blood Vessels / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D004396:Coloring Agents; D006131:Growth Inhibitors / Q000627:therapeutic use*; D006614:Hindlimb; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D009336:Necrosis; D010087:Oxides / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D001152:Arsenicals; D004396:Coloring Agents; D006131:Growth Inhibitors; D010087:Oxides; D011838:Radiation-Sensitizing Agents; D000077237:Arsenic Trioxide