In vitro studies on the cardiotoxicity of chemotherapeutics.

The de novo synthesis of 'shock proteins' is a cellular reaction towards toxic agents. Therefore, the induction of 'shock proteins' serves as a detector of toxicity on the level of protein synthesis. We investigated the effects of chemotherapeutics on cultured cardiac myocytes with this test system. Cisplatin (greater than or equal to 16 mumol/l) and methotrexate (greater than or equal to 1.4 mumol/l) evoked the de novo formation of a 30-kilodalton 'shock protein'. Doxorubicin (80-0.8 mumol/l) and daunomycin (90-0.9 mumol/l) inhibited protein synthesis almost completely. The other chemotherapeutic drugs tested did not influence heart cell protein formation even at concentrations widely above the pharmacological range. Our results indicate that the anthracyclines probably exert cardiotoxicity by depression of protein synthesis. Cisplatin and methotrexate are potentially cardiotoxic at high concentrations.