Diarylsulfonylureas and radiotherapy. I. In vitro studies with N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea (Sulofenur).
The effects of proliferative state and environmental factors on the cytotoxicity of N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea (Sulofenur) were examined using EMT6 mouse mammary tumor cells in monolayer cultures. The toxicity of Sulofenur was at least as great in quiescent, plateau phase cultures as in exponentially growing cultures. Acute hypoxia during treatment did not alter the efficacy of the drug. The pH of the culture medium was a critical determinant of cytotoxicity; survival decreased progressively as the pH of the culture medium decreased from 7.0 to 6.0. High concentrations of Sulofenur appeared to potentiate the cytotoxic effects of x-rays. The cytotoxicity of Sulofenur to quiescent cells, the enhanced cytotoxicity at acutely lowered pH, and the interactions between the drug and radiation all suggest that Sulofenur and other diarylsulfonylureas warrant further examination as agents for use in combination with radiotherapy for the treatment of solid tumors.
Rockwell
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Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510.
Grindey
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GB
D000818:Animals; D000970:Antineoplastic Agents; D015687:Cell Hypoxia; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000532:radiotherapy; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D011838:Radiation-Sensitizing Agents; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D013453:Sulfonylurea Compounds; C058179:sulofenur