A Bioassay to Measure Cytotoxicity of Plasma from Patients Treated with Mitomycin C

Raymond S. Marshall, C. Erlichman, A. Michael Rauth

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4 Scopus citations

Abstract

The unpredictable clinical toxicity observed in patients treated with mitomycin C and the observation that this agent must be reduced to an active form before alkylating target molecules have led to the development of a bioassay which is capable of detecting biologically active forms of mitomycin C in the plasma of drug-treated patients. The bioassay makes use of a repair-deficient mutant of Chinese hamster ovary cells, UV-20, which is 40 to 60 times more sensitive to mitomycin C than its wild-type parent. A standard curve relating in vitro cell colony-forming ability of UV-20 versus drug concentration in the plating medium has been determined. Mitomycin C levels in patient plasma as low as 1 ng/ml can be detected, compared to the 5-ng/ml limit of detection obtained with a high-pressure liquid chromatography assay for the parent compound. This assay has been utilized to detect active drug in plasma obtained from patients with colorectal cancer treated with mitomycin C as a single agent. At the completion of drug injection, serial blood samples were collected in heparinized tubes, and aliquots of plasma were extracted and assayed for mitomycin C levels by high-pressure liquid chromatography, diluted and assayed directly for their toxicity for UV-20 cells, or frozen at -20°C to be assayed at a later time. The activity detected by immediate bioassy was stable up to 2 mo in frozen samples. Plasma pharmacokinetics determined by the bioassay in seven patients were no different than those determined by high-pressure liquid chromatography. No stable, cytotoxic species other than the parent compound were detected by the bioassay in the plasma of patients treated with mitomycin C.

Original languageEnglish (US)
Pages (from-to)5939-5943
Number of pages5
JournalCancer research
Volume45
StatePublished - Nov 1 1985

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Marshall, R. S., Erlichman, C., & Rauth, A. M. (1985). A Bioassay to Measure Cytotoxicity of Plasma from Patients Treated with Mitomycin C. Cancer research, 45, 5939-5943.