Use of Tetrahymena pyriformis to Evaluate the Effects of Purine and Pyrimidine Analogs1

SYNOPSIS Eighty‐four purine and pyrimidine analogs were evaluated for growth inhibition of Tetrahymena pyriformis. The most toxic were 2‐fluoroadenine, 2‐fluoroadenosine, 6‐methylpurine, a series of 5‐fluoropyrimidines, and a series of adenine derivatives substituted in the 9‐position. 2‐Fluoroadenine was metabolized to the ribonucleoside triphosphate and was incorporated into nucleic acids; its inhibition of growth was reversed by high levels of adenine. 6‐Methylthiopurine ribonucleoside was phosphorylated, but only to the monophosphate derivative. Contrasting T. pyriformis with mammalian cells gave clues to the mechanism of action of some of the agents. 6‐Mercaptopurine, 6‐methylthiopurine ribonucleoside, and 6‐thioguanine, all potent pseudofeedback inhibitors of de novo purine biosynthesis in mammalian cells, are not toxic to T. pyriformis, which lacks the de novo purine pathway; this implies that inhibition of de novo purine biosynthesis by them underlies their growth inhibition of mammalian cells.