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Polyamines, especially spermine, are very effective in enhancing thermal killing of mammalian cells cultured as a monolayer. The response of EMT6 multicellular tumour spheroids to heat in the presence of spermine was studied using cell survival and growth delay as endpoints. Compared to cells in a monolayer, spheroids were found to be highly resistant to combined heat and spermine. In spite of this, considerable enhancement of thermal killing by spermine was observed when the combined treatment was prolonged for a few hours. These results, together with data obtained using labelled spermine, suggest that difficulties in penetration of spermine into the inner cells of the spheroids contribute to the resistance of the latter. A method of circumventing this difficulty is discussed.

Enhancement of thermal killing by polyamines V. The response of EMT6 multicellular tumour spheroids versus monolayer cells