Usefulness of tirapazamine as a combined agent in chemoradiation and thermo-chemoradiation therapy at mild temperatures: reference to the effect on intratumor quiescent cells.

Abstract

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. The mice then received one of six different DNA-damaging agents with or without mild temperature hyperthermia (40 degrees C, 30 min, MTH). These agents were adriamycin (ADM), mitomycin C (MMC), cyclophosphamide (CPA), bleomycin (BLM), cisplatin (CDDP), and tirapazamine (TPZ). After the drug treatment, the tumor-bearing mice were irradiated with a series of doses of gamma-rays. Immediately after irradiation, the tumors were excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling ( = quiescent (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 had not been pretreated with BrdU. MTH significantly increased the MN frequency of total cells in tumors irradiated with gamma-rays combined with CPA, BLM, CDDP or TPZ, and that of Q cells in tumors irradiated with gamma-rays combined with BLM or TPZ. The sensitivity difference in the MN frequency between total and Q tumor cells was significantly decreased by the combination with TPZ. TPZ combined with radiotherapy and TPZ combined with thermo-radiotherapy at mild temperatures appear to be promising modalities for sensitizing tumor cells in vivo, including Q tumor cells.

• Authors: S I Masunaga, K Ono, M Suzuki, Y Kinashi, M Takagaki, H Hori, S Kasai, H Nagasawa, Y Uto
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 91 Issue 5 Pg. 566-72 (May 2000) ISSN: 0910-5050 [Print] Japan
• PMID: 10835503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Radiation-Sensitizing Agents
• Triazines
• Bleomycin
• Tirapazamine
• Mitomycin
• Doxorubicin
• Cyclophosphamide
• Bromodeoxyuridine
• Cisplatin

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Bleomycin (administration & dosage)
• Bromodeoxyuridine
• Carcinoma, Squamous Cell (drug therapy, radiotherapy, therapy)
• Cisplatin (administration & dosage)
• Combined Modality Therapy
• Cyclophosphamide (administration & dosage)
• Dose-Response Relationship, Radiation
• Doxorubicin (administration & dosage)
• Hyperthermia, Induced (methods)
• Mice
• Mice, Inbred C3H
• Micronucleus Tests
• Mitomycin (pharmacology)
• Radiation-Sensitizing Agents (pharmacology)
• Tirapazamine
• Triazines (pharmacology)