Toxic variability and radiation sensitization by Pt(II) analogs in Salmonella typhimurium cells

Journal Article · Sat Sep 01 04:00:00 EDT 1984 · Radiat. Res.; (United States)

DOI:https://doi.org/10.2307/3576335· OSTI ID:6470843

Richmond, R C; Khokhar, A R; Teicher, B A; Douple, E B

A rationale is presented for the development of toxic, i.e., cytocidal, antitumor drugs as clinical hypoxic cell radiation sensitizers. Pt(II) complex-induced hypoxic cell radiation sensitization may occur from Pt(II) complex in free solution and Pt(II) bound to DNA. Although both the free solution and the bound compartments may operate, the free solution compartment is more likely amenable to experimental and clinical control in the case of systemically active Pt drugs. Assuming equivalent cell uptake of different Pt(II) complexes, the free solution compartment of Pt(II) sensitization can be increased by utilizing less toxic analogs of the antitumor drug cis-dichlorodiammineplatinum(II). One such less toxic Pt(II) sensitizer currently in clinical use is found to be cis-(1,1-cyclobutanedicarboxylato)diammineplatinum(II). A new finding of both clinical and mechanistic usefulness is described: irradiation of hypoxic solutions of four cis-Pt(II) complexes, but not two trans-Pt(II) complexes, creates products that cause toxicity in excees of the unirradiated solutions.

• Research Organization: Dartmouth-Hitchcock Medical Center, Hanover, NH
• OSTI ID: 6470843
• Journal Information: Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 99:3; ISSN RAREA
• Country of Publication: United States
• Language: English

Related Subjects

550700 -- Microbiology
560131* -- Radiation Effects on Microorganisms-- Basic Studies-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BACTERIA
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CELL KILLING
COMPLEXES
MICROORGANISMS
PLATINUM COMPLEXES
RADIATION EFFECTS
RADIOINDUCTION
RADIOSENSITIVITY EFFECTS
SALMONELLA
SALMONELLA TYPHIMURIUM
SURVIVAL CURVES
TOXICITY
TRANSITION ELEMENT COMPLEXES