DNA synthesis inhibition and transmembrane permeation into tumor cells by various dialkyl phthalates upon hyperthermia.

Diisobutyl-, dibutyl-, and dioctyl phthalates, at a concentration of 50 microM, markedly inhibited the incorporation of [3H]thymidine into DNA in tumor cells and also cell proliferation. The inhibitions were synergistically enhanced by hyperthermia at 42 degrees C for 1 h. In contrast, dimethyl-, and diethyl phthalates induced almost no inhibition. The effective phthalates were detected in the cells by gas-liquid chromatography, whereas the non-effective drugs were not or were little detected, suggesting involvement of permeability through cell membrane in cytotoxic effects. Combination of the cytotoxic phthalic acid esters and hyperthermia is suggested to be an advantageous treatment for cancer.