Expression of a Novel N-Acetylglucosaminyltransferase in Rat Hepatic Nodules
The hallmark of liver cancer research in recent years has been the development of experimental models by which initiation, promotion and progression phases can be studied1–4. Even though several agents act as promoters, yet many of them are organ specific. Nonetheless, promotion by orotic acid is elegant in that by selecting the initiating carcinogen both cancer in the liver5,6 as well as intestine7 can be achieved. Being an intermediate in the de novo biosynthesis of pyrimidine nucleotides, orotic acid is rapidly metabolized by the liver to uridine nucleotides, which on accumulation creates an imbalance in the pool sizes of nucleotides. Interestingly, promotion by orotic acid can be reversed either by blocking the conversion of orotic acid into uridine nucleotides or by trapping the accumulated uridine nucleotides8. These observations suggest that the pool sizes of nucleotides may have an important role in the promotion phase of the carcinogenic process. An understanding of the metabolic principles underlying orotic acid induced tumor promotion therefore requires a study on the effect of an imbalance of nucleotides on macromolecular biogenesis involving a template process such as nucleic acid synthesis or a non-template process like glycosylation. Glycosylation being a non-template process is regulated by a number of factors including the level and availability of nucleotide sugars.
KeywordsOrotic Acid Hepatic Nodule Baby Hamster Kidney Cell Glycoprotein Synthesis Uridine Nucleotide
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