Mechanism of actinomycin D-induced resistance in Ridgway osteogenic sarcoma: an ultrastructural study.

The ultrastructural appearances of actinomycin D treated sensitive and resistant sublines of Ridgway osteogenic sarcoma (ROS) have been correlated with the suggested mechanism of drug-induced resistance. The resistant subline (designated ROS/ADX/G2) was developed by repeated suboptimal treatment of tumor bearing animals and passage of the fastest growing tumors. In the present experiments, animals bearing sensitive and resistant tumors were given a single intraperitoneal injection of actinomycin D (0.3 microgram/g) and examined at 1, 6 and 24 h after injection. The principal effect of actinomycin D treatment in both cell lines was the development of nucleolar segregation. This change, however, followed a different time-scale in each case, appearing more prominently at an early stage and returning more quickly to normal in the actinomycin D resistant cell line. These findings can be interpreted as being in agreement with the suggestion that reduced drug retention or an increased rate of detoxification provides the mechanism of acquired resistance.