Variant Chinese hamster cells resistant to the proline analogl-azetidine 2-carboxylic acid

Variants resistant to the toxic effects of the proline analogl-azetidine 2-carboxylic acid (AZCA) have been isolated from the Chinese hamster tissue culture line G3 by a three-step selection procedure using increasing concentrations of AZCA. Cells surviving each of the three selective steps have been examined for AZCA resistance and for proline uptake, biosynthesis, and degradation. The largest increment in AZCA resistance is acquired in the third step and is due to overproduction of proline as a result of increased activity of the enzyme system responsible for the conversion of glutamic acid to glutamic γ-semialdehyde. It is not accompanied by an increase in the rate of formation of proline from ornithine or in the rate of proline uptake or degradation.