Influence of irinotecan and SN-38 on the irradiation response of WHO3 human oesophageal tumour cells under hypoxic conditions.
Irinotecan and its metabolite SN38 were evaluated for their cytotoxicity and influence on radiosensitivity in WHO3 human oesophageal cells under hypoxic conditions. The IC50's of Irinotecan and SN-38 were found to be 0.8 and 0.04 microM, repectively, with SN-38 emerging as the more potent drug. The toxicities were similar under anoxic conditions. Given in conjunction with irradiation under hypoxic conditions, the two drugs restored the radiosensitivity of WHO3 cells in a dose-dependent manner by factors of 1.5-2.1 as compared to a control oxygen enhancement ratio (OER) of 2.1 in this cell system. In the subtoxic concentration range of 10(-2) microM SN-38 still generated a marked sensitisation of hypoxic tumour cells by factors of 1.2-1.6. It is concluded that the topoisomerase inhibitor Irinotecan and in particular the metabolite SN-38 may be clinically useful for radiotherapy of notoriously hypoxic tumour pathologies.
Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
C E J
CE
Van Rensburg
J P
JP
Slabbert
L
L
Bohm
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D000077146:Irinotecan; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D000077146:Irinotecan; D002166:Camptothecin