DIFFERENCES IN THE INHIBITION OF TRANSLATION BY CISPLATIN, TRANSPLATIN, AND CERTAIN RELATED-COMPOUNDS

The non-therapeutic cisplatin congeners transplatin and chloroethylene triamine platinum (dien) inhibited translation to a similar extent as cisplatin did. The IC50 values were: cisplatin 23 mu M, transplatin 54 mu M, and dien 117 mu M. Unlike certain heavy metal inhibitors of tra nslation, the effect of neither cisplatin nor the congeners was revers ed by 3':5'-cyclic adenosine monophosphate (cAMP). This suggests that the effect of these platinum compounds does not occur by the heavy met al mechanism. Polyribosomes and ribosomal subunits formed in transplat in-inhibited reactions differed from those in reactions inhibited by c isplatin. Specifically, large polyribosomes and complete 80S ribosomal subunits accumulated in the presence of transplatin. This indicates t hat while cisplatin slowed initiation of peptide synthesis, the trans- isomer slowed elongation. Substantive differences were not found betwe en cisplatin and the monofunctional compound dien. This congener incre ased the non-peptidyl disintegrations per minute in the acid precipita tes of assays containing [(35)]methionine. The high background indicat ed that an interaction between the label and a precipitable component of the system was induced by dien. However, consumption of methionine by this interaction did not appear to be the cause of the inhibition. Although there may be differences in the mechanisms of the effects, th e finding that the non-therapeutic congeners inhibit translation at si milar concentrations as cisplatin suggests that this inhibition is not responsible for the anticancer effect. On the other hand, the possibi lity that decreased translation could play an important role in the to xicity of these compounds in certain quiescent cells cannot be ruled o ut. Copyright (C) 1996 Elsevier Science Inc.