K. Iwamoto, D. Martin
Nov 15, 1974
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Influential Citations
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Quality indicators
Journal
Biochemical pharmacology
Abstract
Abstract We compared the effects of two chemically similar purine analogs, 4-hydroxypyrazolo(3,4-d)pyrimidine (allopurinol) and 4-aminopyrazolo(3,4-d)pyrimidine (4-APP) on the growth and on de novo purine biosynthesis of rat hepatoma cells in culture. Both compounds were found to significantly inhibit their growth as well as their de novo purine synthesis, thesis, the effective concentrations of 4-APP being nearly two orders of magnitude less than those of allopurinol. For both drugs, there was a good correlation between the ability to inhibit de novo purine synthesis and to produce growth inhibition, suggesting a causal relationship. Although the two compounds inhibit purine synthesis to a similar extent, the mechanisms by which they affect the early portion of the purine pathway differ: allopurinol apparently acts by end product-mediated inhibition and/or depletes the cell of substrates, whereas 4-APP, in addition, regulates gene expression by causing a repression of an early function in the de novo pathway.