Actinomycin resistance in cultured hamster cells.

A cell line derived from a malignant hamster tumor was made resistant to 1/ag/ml actinomycin D by continuous exposure to increasing concentrations of the antibiotic. In addition to a normal nucleolus, the resistant cells exhibited several small exhausted ones in the terminal phase of nucleolar segregation. Comparative growth rate and incorporation of uridine-3H revealed a significant delay in the resistant line as compared with the sensitive one, although the same sequence of incorporation was found qualitatively within the nucleolus and the nucleus. Cross-resistance was present in resistant cells with Nogalamycin and Chromomycin, two antibiotics with a mode of action similar to actinomycin but chemically unrelated. Incorporation of actinomycin D-3H was studied by high-resolution radioautography: radioactivity was found in the chromatin of resistant cells although in lower amounts than in sensitive cells. According to other experiments, actinomycin penetration was thought to be altered in resistant HeLa and B. subtit is cells. In the present case, the resistance is considered likely to result from a successive derepression of secondary organizers and/or the development of an enzymatic mechanism for inactivation of actinomycin inside the cell.