Abstract
Variants resistant to canavanine, an arginine analogue, have been isolated from two long-term human lymphoblastoid cell lines. They are 20-fold more resistant to canavanine than the parental lines and this phenotype is stable in the absence of canavanine for more than 100 generations. The specific activity of argininosuccinate synthetase, the first of two enzymes necessary for the conversion of citrulline to arginine, is elevated in variants from both cell lines. Furthermore, this enzyme activity is refractory to the repression caused by arginine in normal lymphoblasts. The specific activity of argininosuccinate lyase, the second enzyme in the pathway from citrulline to arginine, is not appreciably changed. Arginine uptake appears normal in the variants since they grow as well as the parental lines in media containing a wide range of arginine concentrations. Arginyl-tRNA synthetase activity is also unchanged. Thus the canavanine-resistant variants have altered control of at least one urea cycle enzyme and appear to be regulatory mutants of human cells.
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Jacoby, L.B. Canavanine-resistant variants of human lymphoblasts. Somat Cell Mol Genet 4, 221–231 (1978). https://doi.org/10.1007/BF01538986
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DOI: https://doi.org/10.1007/BF01538986