The immunopotentiation effects of the bifunctional radiosensitizer KIN-806 in comparison with its analogs KIN-804 and KIN-844.
KIN-806 is one of the 2-nitroimidazole derivative hypoxic cell radiosensitizers. Its radiosensitizing effects and the degree of lung metastasis detected were evaluated and compared with its analogs KIN-804 and KIN-844. The immune reactions induced by these radiosensitizers were also analyzed. Female C3H/He mice and SCCVII tumor cells were used. Seventeen days after inoculation of SCCVII tumor cells into the animals, 0.4 g/kg of KIN-806, KIN-804, and KIN-844 was administered to each radiosensitizer group 30 min before 40 Gy was delivered as local irradiation. In each group, KIN-806, KIN-804, and KIN-844 markedly suppressed tumor regrowth in comparison with animals that received irradiation alone. There was no significant difference in the radiosensitizing effects among these three radiosensitizers. A marked suppression of lung metastasis and macrophage/T-lymphocyte infiltration into the tumor were observed only in the KIN-806-administered groups, regardless of the presence or absence of radiation therapy. It therefore appears likely that the lung metastasis suppression was caused by the immune reaction elicited by KIN-806, which is an excellent immunopotentiator as well as an effective radiosensitizer.
Inomata
T
T
Department of Radiology, Kochi Medical School, Kohasu, Oko-cho, Nankoku-city, Kochi 783-8505, Japan.
Ogawa
Y
Y
Nishioka
A
A
Hamada
N
N
Ito
S
S
Kariya
S
S
Yoshida
S
S
Nagasawa
H
H
Hori
H
H
Inayama
S
S
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000532:radiotherapy / Q000556:secondary; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy; D009593:Nitroimidazoles / Q000008:administration & dosage*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*
D006877:Hydroxamic Acids; C121164:KIN 806; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C076264:2-nitroimidazole-1-methylacetohydroxamate