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cis-Diamminedichloroplatinum(II)-induced Sister Chromatid Exchange: An Indicator of Sensitivity and Heterogeneity in Primary Human Tumor Cell Cultures¹

The Department of Experimental Radiotherapy, The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Houston, Texas 77030 [P. J. T., C. M. V., W. A. B.]; LifeTrac, Irvine, California 92715 [F. L. B.]; and The Brain Tumor Research Center of the Department of Neurological Surgery, School of Medicine, University of California, San Francisco, California 94143 [D. F. D.]

The effect of cis-diamminedichloroplatinum(II) (cPt) on sister chromatid exchange (SCE) induction was determined in 13 human primary tumor cell cultures. Primary cultures were derived from surgical specimens of solid tumors composed of a variety of histologies. Three to 16 days after biopsy, depending on the growth rate, cultures were treated with graded concentrations of cPt for 1 h and the SCE assay was performed. SCE dose-response curves (SCEs induced per chromosome versus cPt concentration) showed a wide range in cPt sensitivities that was not dependent on histology. SCE frequency histograms showed that several of the primary cultures contained both cPt-sensitive and-resistant cells. For six of the cultures, the SCEs induced per chromosome at 15 µM cPt were plotted versus the IC₉₀ determined from a survival assay. A line fit to those points yielded a correlation coefficient of -0.74. These results show a relationship between the activity of cPt in the SCE assay and in the survival assay, which suggests that SCE analysis may be useful for predicting cPt sensitivity. In addition, characterization of cellular heterogeneity in cPt sensitivity using the SCE assay may provide additional information useful in the prediction of tumor response to treatment.

¹ Supported by NIH Grant CA-06294.

² To whom requests for reprints should be addressed, at University of Texas Cancer Center, M. D. Anderson Hospital, Experimental Radiotherapy-66, 6723 Bertner Avenue, Houston, TX 77030.

Received 6/ 6/86. Revised 8/19/86. Accepted 8/22/86.