This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Borek, E. Articles by Waalkes, T. P. Search for Related Content PubMed PubMed Citation Articles by Borek, E. Articles by Waalkes, T. P.

High Turnover Rate of Transfer RNA in Tumor Tissue¹

Department of Microbiology, University of Colorado Medical Center, Denver, Colorado 80262 [E. B., B. S. B.]; University of Missouri, College of Agriculture, Columbia, Missouri 65201 [C. W. G., C. W. K.]; New York University Medical Center, Institute of Environmental Medicine, New York, New York 10016 [S. B., W. T.]; and Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205 [T. P. W.]

Cancer patients and tumor-bearing animals excrete high levels of modified purines and pyrimidines some of which, e.g., N₂,N₂-dimethylguanosine, can originate only from transfer RNA (tRNA). Until recently, it could not be ascertained whether the high level of excretion of such compounds is due to cell death or specific tRNA turnover. However, an approach to this problem became feasible, with ß-aminoisobutyric acid as a probe. This compound is a terminal degradation product of thymine which is present in both DNA and tRNA. Since the pathway of synthesis of thymine is different in the two macromolecules, it and its end product, ß-aminoisobutyric acid can be differentially labeled with [¹⁴C]formate and [³H₃]methylmethionine as precursors. Therefore the ratio of the two labels in the excreted ß-aminoisobutyric acid is a measure of the macromolecular origin of the degradation product. We have found from such analysis that tRNA's are not homogeneous in their turnover rate. There is a subpopulation that turns over much faster than the rest. The turnover rate of a subpopulation of tRNA's in tumor tissue exceeds the turnover rate of tRNA's in normal tissue. Such rapid degradation of tRNA's must be the source of the massive excretion of modified nucleosides by cancer patients which can be 10-fold higher than in normal subjects.

¹ This work was supported by NIH Contract N01-CM-12186-04, National Cancer Institute Grants 15315 and 13343, and National Institute of Environmental Health Services Grant ES 00260.

² To whom requests for reprints should be addressed, at the Department of Microbiology and Immunology, University of Colorado Medical Center, 4200 East Ninth Avenue, Denver, Colo. 80262.

Received 12/17/76. Accepted 6/ 8/77.

This article has been cited by other articles:

				D. M. Thompson, C. Lu, P. J. Green, and R. Parker tRNA cleavage is a conserved response to oxidative stress in eukaryotes RNA, October 1, 2008; 14(10): 2095 - 2103. [Abstract] [Full Text] [PDF]

				M Litt and K Weiser Histidine transfer RNA levels in Friend leukemia cells: stimulation by histidine deprivation Science, August 11, 1978; 201(4355): 527 - 529. [Abstract] [PDF]