PMID: 3755716Jul 1, 1986Paper

Studies on the toxicity of RSU-1069

International Journal of Radiation Oncology, Biology, Physics
G F Whitmore, S Gulyas

Abstract

RSU-1069 combines an aziridine function with a 2-nitroimidazole and has been reported to exhibit extraordinary radiosensitization both in vitro and in vivo. Such sensitization appears to be at variance with the electron affinity of the compound. In addition, recent experiments suggest that the compound is highly toxic to hypoxic tumor cells in vivo. On the assumption that the observed radiosensitizing ability may be a manifestation of toxicity and because of the high in vivo toxicity, we have investigated aerobic and hypoxic toxicity, both in wild type CHO cells and in mutants sensitive to a variety of DNA damaging agents. With wild type cells under aerobic conditions, the compound is approximately 50 times as toxic as misonidazole and under hypoxic conditions, approximately 250 times as toxic. The ratio of hypoxic to aerobic toxicity is approximately 80 times. Under aerobic conditions, repair-deficient mutants are 10 times as sensitive to RSU-1069 as wild type cells and approximately 100 times as sensitive under hypoxic conditions. The ratio of hypoxic to aerobic toxicity for the mutant cells is approximately 900. Based on these observations, we suggest that under aerobic conditions the aziridine function is primarily responsi...Continue Reading

References

Mar 10, 1971·Nature: New Biology·C P StannersH Green
Jan 15, 1971·International Journal of Cancer. Journal International Du Cancer·T A Connors, D H Melzack
Aug 1, 1981·Chemico-biological Interactions·A J Varghese, G F Whitmore
May 1, 1980·Somatic Cell Genetics·L H ThompsonK Brookman

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Citations

Jan 1, 1991·Mutation Research·D A Widdick, D I Edwards
Jan 1, 1992·International Journal of Radiation Oncology, Biology, Physics·S ColeJ Sebolt-Leopold
Feb 9, 2000·Toxicology and Applied Pharmacology·A E Lee, W R Wilson
Jul 1, 1991·International Journal of Radiation Biology·P G BraunschweigerP Furmanski
May 7, 2021·Frontiers in Pharmacology·Yue LiXiao-Feng Li

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