Tumor-Specific tRNA Modifications in Mouse Plasmacytomas and Other Tumors

Abstract

We have been studying the tRNA populations in mineral-oil-induced, immunoglob-ulin-seereting Balb/c mouse plasmacytomas (Potter 1972) for more than a decade in an attempt to determine if these “adaptor” molecules, which are essential to protein synthesis, play a role in regulating or modulating protein synthesis or in affecting the amino acid sequence of the product of this synthesis. From the outset we were struck by the large number of isoaccepting species of aa-tRNA molecules that sensitive separation techniques revealed for each amino acid. Not only did amino acids such as tryptophan that have one code word frequently have more than one isoaccepting tRNA, but as many as nine peaks of seryl-tRNA were identified for serine, which has six code words (Mushinski 1971). This redundancy of isoaccepting tRNAs was more obvious in the plasmacytomas than in normal tissues. In addition, we found a remarkable number of differences, both quantitative and qualitative, in the aa-tRNA chromatographic patterns when different plasmacytomas were compared. The comparisons were dqne in pairs by separately aminoacylating tRNA from two different tissues or tumors with ³H-or ¹⁴C-labeled amino acid, mixing them, and cochromatographing them on reversed phase columns (RPC-2, as shown in Fig. 1, or RPC-5, as shown in Figs. 2 and 3). The chromatographic pattern of aa-tRNA was not affected by the source of enzymes, and a standard preparation of aa-tRNA synthetase from liver was used in all reactions.

We thank Drs. Aldo Spizzichino and James Koziol for their collaboration in computer and statistical analyses, Mr. William Muldoon for expert laboratory assistance, Drs. Dolph Hatfield and Dezider Grunberger for helpful discussions, Drs. Dolph Hatfield and Carol Thiele for a thoughtful reading of this article, and Ms. Victoria Armstrong for expert preparation of the manuscript