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Correlation of Transfer RNA Methylase Activity with Growth and Differentiation in Normal and Neoplastic Tissues

Section on Cellular Control Mechanisms, Human Tumor Cell Biology Branch, National Cancer Institute, Bethesda, Maryland 20014

RNA methylase activities were measured in several different biological systems in an attempt to correlate the level of enzyme activity with cell growth and differentiation or neoplasia per se.

RNA methylase activity was identical in blast cells grown in long-term tissue culture and originally derived from the peripheral blood of normal patients and from patients with various hematological cancers. The activity of the homogenates of both groups was 50% lower when harvested in stationary as opposed to logarithmic phase of growth.

Human lymphocytes, obtained from the peripheral blood of normal donors, which were not propagated in tissue culture and not "in cycle," had low activity. However, after stimulation with the mitogen, phytohemagglutinin, a 3-fold induction occurred, resulting in levels comparable to those observed in the tissue culture lines.

Low and similar tRNA methylase activity was observed in bone marrow from normal individuals and patients with chronic myelocytic leukemia when marrow differentials revealed equivalent levels of cellular differentiation. However, the activity was 3-fold higher in leukemic marrows when the percentage of primitive cells (myeloblasts) was greater than 40%.

Although activity was 10-fold higher in spleen from leukemic AKR mice compared to normal AKR mice, activity was not directly correlated with growth rate since the levels were identical in different groups of AKR leukemic cells over a 10-fold difference in growth rate.

Similarly, the activity was identical in two histologically similar spontaneous murine mammary tumors differing in growth rate. However, as with the tissue culture cells, activity in both sublines was lower in stationary as opposed to logarithmic phase growth.

The data suggest that (a) increased tRNA methylase activity, possibly including qualitatively different enzymes, is characteristic of immature normal cells as well as neoplastic cells; (b) the increase is dependent upon the percentage of cells in cycle; and (c) once fully expressed, tRNA methylases of neoplastic cells do not increase further with an increase in growth rate.

¹ To whom reprint requests should be addressed at Building 10, Room 6B17, National Cancer Institute, Bethesda, Md. 20014.

Received 2/27/70. Accepted 6/ 9/70.