Transfer RNA methylase and transfer RNA methylase-inhibitor activity in normal and malignant human ovarian tissue.

Summary Eight different human ovarian carcinomas were shown to have 2 to 25 times higher transfer RNA methylase-specific activity and transfer RNA methylating capacity than do normal ovarian tissues. The more rapidly metastasizing, poorly differentiated carcinomas had higher transfer RNA methylase activity than did slower metastasizing, well-differentiated, and intermediately differentiated carcinomas. The transfer RNA methylase activities of all the ovarian tissues, normal and malignant, were demonstrated to be directly related to the activity of an endogenous transfer RNA methylase inhibitor; the higher the enzyme activity, the lower the inhibitor activity. Experiments showed that the intermediately differentiated carcinomas and the normal ovarian tissue had the following analogous biochemical characteristics. They produced similar methylation patterns with an exogenous transfer RNA substrate, and they were unable to methylate their own endogenous transfer RNA or that of the others. The poorly differentiated carcinomas differed from normal ovarian tissue in that they synthesized greater percentages of methylated guanine residues compared with the other methylated bases, they contained barely detectable amounts of an endogenous transfer RNA methylase inhibitor, and they were capable of methylating transfer RNA isolated from normal ovarian tissue but not their own endogenous transfer RNA.