Pactamycin resistance in CHO cells: Morphological changes induced by the drug in the wild‐type and mutant cells

Stable mutants resistant to pactamycin (PacR), a polypeptide chain initiation inhibitor, have been selected in a single step in Chinese hamster ovary (CHO) cells. The sensitivity of protein synthesis in mutant cell extracts to pactamycin indicates that resistance involves an alteration in the permeability of this drug. The failure of PacR mutants to show cross-resistance to other compounds provides further indication that the lesion is presumably specific for pactamycin. Cell hybrids formed between PacR X PacS lines show intermediate sensitivity towards pactamycin, suggesting that the PacR lesion behaves codominantly under these conditions. In the presence of subinhibitory concentrations of pactamycin, CHO cells, which are normally short, polygonal and disoriented, became greatly elongated and aligned themselves in parallel fashion to produce highly oriented colony morphologies, reminiscent of normal diploid fibroblasts. This effect of pactamycin on cellular morphology was seen much more clearly with the PacR mutants, although somewhat higher concentrations of the drug were required to produce this change.