Chemical Carcinogen-Induced Changes in tRNA Metabolism in Human Cells
Abstract
It was proposed that changes in tRNA metabolism are required for cells to progress through the stages of carcinogenesis, and a comprehensive hypothesis was formulated to describe tRNA-mediated endogenous promotion of carcinogenesis. This hypothesis offers a viable explanation for the lengthy time frame observed between carcinogen exposure and neoplastic transformation. A role was defined for 7-methylguanine as an endogenous promoting agent, whereby this natural RNA catabolite induces queuine hypomodification in the tRNA anticodon by inhibiting the queuine insertion enzyme tRNA-guanine ribosyltransferase. Subsequently, 7-methylguanine induces neoplastic transformation. A cell culture system was developed which allows the study of tumor promoter-induced mimicry of transformation with normal human cells, and using this system, phorbol ester tumor promoters were also demonstrated to induce queuine hypomodification of TRNA. However, in this case, the hypomodification occurred due to a specific phorbol ester inhibition of queuine transport into the cells. Most importantly, overcoming the tumor promoter-induced hypomodification of tRNA by supplying the cells with excess queuine, blocked the expression of a transformed phenotype by the human cells. Therefore, queuine may be an anti-promoting compound, and a role for queuine hypomodification in the expression (promotion) of carcinogenesis appears likely.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 20, 1984
- Accession Number
- ADA150962
Entities
People
- R. W. Trewyn
Organizations
- Ohio State University