Toxicity testing in vitro. II. Use of a microsome – cultured human fibroblast system to study the cytotoxicity of cyclophosphamide

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Abstract
The toxicity of cyclophosphamide (CP), has been studied using a human fibroblast cell culture system. A method is described in which CP is incubated with liver microsomes and appropriate co-factors before addition to the cells. This permits activation of the CP to its cytotoxic metabolite but avoids the necessity of adding microsomes directly to the cell culture. It was demonstrated that under these conditions CP was irreversibly toxic to the cells within hours at dose levels ≥ 0.3 mg/ml. In the absence of microsomal activation it was toxic at similar dose levels but the toxic effects required several days to develop.