PMID: 3755712Jul 1, 1986Paper

Studies on the mechanisms of the radiosensitizing and cytotoxic properties of RSU-1069 and its analogues

International Journal of Radiation Oncology, Biology, Physics
J M WallingE M Fielden

Abstract

RSU 1069 is a substantially more efficient sensitizer than misonidazole when hypoxic Chinese hamster V79 cells are irradiated in vitro at room temperature; such that for 0.5 mmol dm-3 sensitizer an ER of 3.0 is obtained for RSU 1069 whereas an ER of only 1.6 is obtained for misonidazole. However, when irradiation is done at 4 degrees C, the radiosensitization caused by RSU 1069 is reduced to a level close to that obtained with misonidazole, the action remaining unaltered at the lower temperature. This temperature dependent component of sensitization for RSU 1069 suggests the involvement of a slow biochemical process that has an appreciable activation energy. The RSU 1069 analogue RB 7040 is a more efficient radiosensitizer than RSU 1069 particularly at lower concentrations. This compound has a pKa value of 8.45, in contrast to that of RSU 1069 which is 6.04. Weak bases with pKa values in excess of average intra-cellular pH can be taken up preferentially into cells from medium at pH 7.4. It is shown that RB 7040 has a 4 X higher intracellular concentration than RSU 1069 for a similar extracellular concentration. This will explain, at least in part, the greater sensitizing efficiency of this compound when compared to RSU 1069 in ...Continue Reading

References

Jun 1, 1985·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·M F DennisM E Watts
Jun 1, 1985·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·M E Watts, N R Jones
Aug 1, 1984·International Journal of Radiation Oncology, Biology, Physics·P Workman, M I Walton

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Citations

Apr 1, 1989·International Journal of Radiation Oncology, Biology, Physics·P O'Neill, S M Cunniffe
Apr 1, 1989·International Journal of Radiation Oncology, Biology, Physics·S Dische
Apr 1, 1989·International Journal of Radiation Oncology, Biology, Physics·P WardmanJ White
Sep 1, 1988·The British Journal of Radiology·N Chalmers, J Best
Sep 1, 1988·The British Journal of Radiology·P Siem-Jørgensen
Dec 1, 1986·The British Journal of Radiology·A HorwichM J Peckham
Apr 21, 1998·Toxicologic Pathology·M A BreiderA W Gough
Apr 1, 1988·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·J WallingM A Stephens
Oct 28, 1998·Toxicologic Pathology·M A BreiderA W Gough
Aug 1, 1987·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·K R AustenE M Fielden

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