SPECIFIC LACK OF THE HYPERMODIFIED NUCLEOSIDE, QUEUOSINE, IN HEPATOMA MITOCHONDRIAL ASPARTATE TRANSFER-RNA AND ITS POSSIBLE BIOLOGICAL SIGNIFICANCE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (3) , 1167-1171
Abstract
Tumor nucleic acids are frequently deficient in methylated and other modified nucleotides. In particular, cytoplasmic transfer RNA (tRNA) from various neoplasms partially lack the hypermodified nucleoside queuosine, a modification specific for anticodons of histidine-, tyrosine-, asparagine- and aspartic acid-accepting tRNA. Using aspartate tRNA as an example, liver mitochondria contain tRNA fully modified with respect to queuosine, while the corresponding tRNA from mitochondria of Morris hepatoma 5123D completely lacks this constituent. The sequences of these tRNA, which were determined by a highly sensitive 32P-postlabeling procedure entailing the direct identification of each position of the polynucleotide chains, were .**GRAPHIC**. Lack of queuosine in the hepatoma mitochondrial tRNA may be due to the invariability of queuine in the hepatoma mitochondria for incorporation into tRNA or to inhibition of the modifying enzyme, tRNA (guanine)-transglycosylase, in the tumor. Taking into account results of others indicating a possible involvement of the queuosine modification in differentiation of eukaryotic cells, the queuosine defect may develop at an early stage of carcinogenesis (i.e., during the promotion phase) and be directly involved in abnormalities of mitochondria which have been observed frequently in transformed cells and tumors.