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| DETECTION OF HYPOXIA BY MEASUREMENT OF DNA-DAMAGE IN INDIVIDUAL CELLS FROM SPHEROIDS AND MURINE TUMORS EXPOSED TO BIOREDUCTIVE DRUGS .2. RSU-1069 |
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| Author(s): OLIVE PL |
| Source: BRITISH JOURNAL OF CANCER Volume: 71 Issue: 3 Pages: 537-542 Published: MAR 1995 |
| Times Cited: 21 References: 25 |
| Abstract: The ability of the dual-function bioreductive drug, RSU 1069, to identify hypoxic cells in multicell spheroids and murine SCCVII squamous cell carcinomas was examined using the alkaline comet method. This method applies fluorescence microscopy and image analysis to measure the amount of migration of DNA from individual cells embedded in agarose and exposed to an electric field. Chinese hamster V79 spheroids, exposed for Ih to RSU 1069, were disaggregated and individual cells were analysed for DNA damage. Following exposure to RSU 1069, aerobic cells exhibited DNA single-strand breaks while DNA interstrand cross-links were produced in hypoxic cells. Spheroids containing 40-50% radiobiologically hypoxic cells exhibited 20-30% cells with cross-links and the remainder showed only strand breaks. Similar patterns of damage were observed in SCCVII rumours growing in C3H mice exposed to 25-200 mg kg(-1). Subsequent irradiation of cells in vitro greatly improved the distinction between aerobic and hypoxic cells from spheroids or SCCVII murine rumours exposed to RSU 1069, especially after treatment with low drug doses. The pattern of damage was relatively stable for at least 4 h after drug injection. Results indicate that detection of hypoxic cells in solid tumours may be practical using this agent or a prodrug, PD 144872, selected for phase I clinical testing as a hypoxic cell radiosensitiser and cytotoxin in human tumours. |
| Document Type: Article |
| Language: English |
| Reprint Address: OLIVE, PL (reprint author), BRITISH COLUMBIA CANC RES CTR, DEPT MED BIOPHYS, 601 W 10TH AVE, VANCOUVER, BC V5Z 1L3 CANADA |
| Publisher: STOCKTON PRESS, HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS |
| Subject Category: Oncology |
| IDS Number: QJ295 |
| ISSN: 0007-0920 |
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