Date of Award

Fall 1989

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry & Biochemistry

Program/Concentration

Chemistry

Committee Director

Mark S. Elliot

Committee Member

Patricia A. Pleban

Committee Member

Roy L. Wiliams

Committee Member

Robert E. Ratzlaff

Call Number for Print

Special Collections LD4331.C45 B74

Abstract

The purpose of this study was to treat normal human fibroblasts with known tumor promoters and observe queuine modification of tRNA. The queuine insertion enzyme, tRNAguanine ribosyltransferase, was studied in vivo and in vitro. Tumor promoter-treated human fibroblast cultures exhibited variable queuine-insertion rates with a transient inhibition that correlated with variable levels of queuine modified tRNA over time in culture from passages 3 — 8. In contrast the in vitro studies showed that phorbol cetera and saccharin actually increased insertion with strong evidence indicating phosphorylation as a positive modulating force of the enzyme activity. It is proposed that chronic stimulation of protein kinase C with tumor promoters leads to increased turnover of protein kinase C and a resulting deficit of the kinase. This would reduce the effect on the insertion enzyme, resulting in undermodified tRNA with time in culture. Therefore, it is proposed that protein kinase C is an important modulator of overall queuine metabolism.

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DOI

10.25777/08c8-t205

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