Accession Number : ADA138715

Title :   Chemical Carcinogen-Induced Changes in tRNA Metabolism in Human Cells.

Descriptive Note : Interim technical rept. 1 Oct 82-30 Sep 83,


Personal Author(s) : Trewyn,R W

PDF Url : ADA138715

Report Date : 30 Nov 1983

Pagination or Media Count : 75

Abstract : It is hypothesized that transfer RNAs mediate endogenous promotion of carcinogenesis subsequent to chemical carcinogen initiation, and that without the appropriate changes in tRNA metabolism, the ultimate expression of the neoplastic state will not be attained. Current studies are concentrating on tRNA ribosyltransferas modification reactions which are considered to be the pivotal molecular aberrations in this process. A normal human cell culture model system responsive to phorbol ester tumor promoters was developed which allows the evaluation of the role of tRNA in promotion of carcinogenesis. Chronic exposure to the tumor promoters induces a transient 5 to 10-fold increase in the saturation density of human cells if the treatment is initiated at early population doublings in culture in medium supplemented with elevated levels of specific amino acids. A significant decrease in queuine modification in the anticodon of cellular tRNAs precedes the transient 5 to 10-fold increase saturation density, and queuine modification increases prior to the subsequent decrease in saturation density. The increase in queuine modification correlates to the induction of an endogenous queuine salvage pathway. Most importantly, the addition of excess exogenous queuine inhibits the transient increase in saturation density induced by the tumor promoters, i.e., it blocks the expression of a transformed phenotype.

Descriptors :   *Ribonucleic acids, *Carcinogens, Metabolism, Cells(Biology), Humans

Subject Categories : Biochemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE