Summary The effects of the differentiation-inducing polar solvent N-methylformamide (NMF) on artificially induced and spontaneous metastases from a murine hepatocarcinoma (HCA-1) in C3Hf/Kam mice were investigated. Exposure of HCA-1 cells in vitro for 6 days to 1.0% or 1.25% NMF resulted in an increase in the number of lung nodules formed in mice when these cells were injected into their tail veins. This in vitro NMF exposure increased cell volume and induced only a slight amount of cytotoxicity. Administration of NMF to mice I day before i.v. tumour cell inoculation resulted in a dose-dependent increase in the number of lung nodules formed, beginning at an NMF dose of 600mgkg-1. NMF caused a similar magnitude of metastasis enhancement in immunosuppressed mice. However, when the maximum dose tested (1,800 mg kg-') was administered as 6 daily fractions of 300 mg kg-each, no increase in artificial metastases was detected. Administration of NMF to mice one day after i.v. tumour cell injection resulted in a dosedependent decrease in the number of lung nodules. In mice bearing 5-6mm HCA-1 leg tumours, treatment with 6 daily fractions of NMF (300mg kg-each) significantly reduced the number of spontaneous pulmonary metastases, yet had very little effect on the growth of the primary tumour. These data suggest that, in a clinically relevant treatment setting, NMF can reduce metastasis formation.

Summary The ability of the sister chromatid exchange (SCE) assay to detect heterogeneity in intrinsic radiation sensitivity was investigated. In order to identify tumour cell subpopulations, frequency histograms of cis-diamminedichloroplatinum (II) (cPt)-induced SCEs were generated and compared to those from cultures that had been irradiated 96h before drug treatment. The results suggested that subpopulations with different radiosensitivities were present in nine of 18 human primary tumour cell cultures evaluated. When the effects of prior irradiation on the subsequent X-ray survival response and on cPt-induced SCE frequency histograms were compared, a good correlation was obtained between the two assays regarding the prediction of heterogeneity in radioresponse. These results suggest that primary cultures can contain both radiationsensitive and radiation-resistant cells, and thus heterogeneity in intrinsic radiosensitivity may exist in human solid tumours.