Abstract
Recently we have demonstrated that orotic acid (OA), a normal cellular constituent is an efficient promoter of liver carcinogenesis in the rat1–4. Being a precursor of pyrimidine nucleotides, feeding OA results in an increased synthesis of uridine nucleotides in the liver. This increase in uridine nucleotides is associated with a decrease in adenine nucleotides thereby creating an imbalance in the nucleotide pool. It was hypothesized that creation of such an imbalance in the nucleotide pool is an important factor in the mechanism by which OA exerts its promoting effect4,5. One of the significant aspects of this hypothesis is that since each cell has its own nucleotide pool pattern geared to its needs, disruption of this pattern could be one mechanism to achieve promotion in a variety of organs. Indeed OA has been shown to promote carcinogenesis in the duodenum initiated by azoxymethane6.
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Vasudevan, S., Lee, G., Qureshi, I.A., Rao, P.M., Rajalakshmi, S., Sarma, D.S.R. (1988). Studies on Metabolic Perturbations and Tumor Promotion: Glycine Induces the Synthesis of Orotic Acid, a Tumor Promoter and the Expression of Certain Cell Cycle Dependent Genes. In: Feo, F., Pani, P., Columbano, A., Garcea, R. (eds) Chemical Carcinogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9640-7_37
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DOI: https://doi.org/10.1007/978-1-4757-9640-7_37
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