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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Studies of the in vivo and in vitro cytotoxicity of the drug RSU-1069.

The radiosensitizing and cytotoxic properties of the drug RSU-1069, (1-(2-nitro-1-imidazolyl)-3-(1-aziridino)-2-propanol) a 2-nitroimidazole with an aziridine ring in its side-chain, have been examined both in vivo and in vitro. Studies with the KHT Sarcoma or RIF1 tumour indicated that, at doses between 0.04 and 0.16 mg g-1 body wt, the drug was increasingly effective at killing tumour cells when combined with radiation. Cell survival in both tumours following combined RSU-1069 and radiation (1500 or 2000 cGy) treatment was similar when the drug was given 60 min before or immediately after irradiation suggesting that the effect observed was due to hypoxic cell cytotoxicity rather than radiosensitization. Studies with CHO cells in vitro indicated that RSU-1069 was equally as effective as a number of other 2-nitroimidazoles as a radiosensitizer when drug exposure and radiation treatment was given at 4 degrees C. It was substantially more toxic to hypoxic than to aerobic CHO cells (a factor of 90 in dose to give equivalent cell killing) and was much more toxic to CHO cells than misonidazole (a factor of approximately 100 in dose) at 37 degrees C. HeLa cells were more sensitive to RSU-1069 than CHO cells and, under hypoxic conditions, were approximately 20-fold more sensitive to the drug than when aerobic. Prior incubation of hypoxic CHO cells with RSU-1069 at toxic concentrations did not influence the sensitivity of the surviving cells to radiation treatment (i.e. there was no shoulder removal as is observed with misonidazole) nor did prior radiation treatment influence the sensitivity of the surviving cells to drug treatment. Overall the results indicate that RSU-1069 is a highly effective cytotoxic agent for hypoxic cells both in vivo and in vitro but, when drug exposure and radiation treatment are given at 4 degrees C, it is not a more effective sensitizer than other 2-nitroimidazoles.[1]

References

  1. Studies of the in vivo and in vitro cytotoxicity of the drug RSU-1069. Hill, R.P., Gulyas, S., Whitmore, G.F. Br. J. Cancer (1986) [Pubmed]
 
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