Application of a microsomal drug activation system in a human tumor cloning assay.

A commercially available preparation of livers from rats can be used to activate cyclophosphamide and DTIC in vitro. This activation can be done in such a way as to have utility in a soft agar cloning assay. The commercial S-9 fraction contains one or more factors which exert a direct inhibitory effect on the ability of five human tumors and three different cell lines to form colonies in soft agar. The inhibition is eliminated by heating to 56 degrees C and is markedly diminished by low speed centrifugation at 7000 g. This commercially available liver preparation may provide a useful tool to extend the feasibility of clonogenic assays to standard drugs and new investigational drugs whose antitumor activity is dependent upon microsomal activation.