DNA-SYNTHESIS INHIBITION AND TRANSMEMBRANE PERMEATION INTO TUMOR-CELLS BY VARIOUS DIALKYL PHTHALATES UPON HYPERTHERMIA

Diisobutyl-, dibutyl-, and dioctyl phthalates, at a concentration of 5 0 mu M, markedly inhibited the incorporation of [H-3]thymidine into DN A in tumor cells and also cell proliferation. The inhibitions were syn ergistically enhanced by hyperthermia at 42 degrees C for 1 h. In cont rast, dimethyl-, and diethyl phthalates induced almost no inhibition. The effective phthalates were detected in the cells by gas-liquid chro matography, whereas the non-effective drugs were not or were little de tected, suggesting involvement of permeabiliy through cell membrane in cytotoxic effects. Combination of the cytotoxic phthalic acid esters and hyperthermia is suggested to be an advantageous treatment for canc er.