Messenger RNA loses the ability to direct in vitro peptide synthesis following incubation with cisplatin

Inhibition of in vitro translation activity by the chemotherapeutic agent cisplatin has been studied. Peptide synthesis was measured in translation assays prepared from guinea pig and rabbit reticulocyte lysates. There is a concentration- and time-dependent inactivation of translation by cisplatin. Inhibition is nearly maximal after a 30-min exposure. Translation is inhibited by cisplatin at concentrations that have been found after the administration of therapeutic doses. Evidence suggests that the suppression of peptide synthesis is due to an interaction between cisplatin and mRNA. An apparent qualitative difference in the peptide products translated from mRNA exposed to cisplatin is demonstrated. Large peptide products are inhibited to a greater extent than products with faster electrophoretic mobility. Decreased translation activity cannot be explained by digestion of the message by either cisplatin itself or by some contaminant of the drug solution.