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We have isolated variants of Chinese hamster lung (CHL) fibroblasts with decreased sensitivity to the toxic proline analog, L-azetidine-2-carboxylic acid (AZCA). Resistance to AZCA is a stable characteristic of these cell lines since it is maintained after 40 generations in nonselective medium. Two AZCA-resistant cell lines overproduce and excrete more proline than wild-type cells. Furthermore, AZCA rapidly inhibits the synthesis of proline from glutamic acid in wild-type but not the resistant cell lines. These studies suggest that resistance to AZCA in these cell lines is due to an alteration in some component of the proline biosynthetic pathway, possibly a regulatory site that is inhibited by AZCA.
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