The Effects of Actinomycin D and Mitomycin C on Mouse Tumors Explanted to the Chorioallantoic Membrane of the Chick Embryo

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Abstract
Two mouse tumors, the sarcoma 180 and the Ridgway osteogenic sarcoma (ROS), were explanted to the chorioallantoic membrane to the 8 day chick embryo, where they grew successfully. At 12 days of incubation, the tumor-bearing embryos received single injections via the yolk sac, of a tolerated dose of actinomycin D or mitomycin C. The embryos were sacrificed at 18 days and the tumors examined. Mitomycin C inhibited the growth of the sarcoma 180 and ROS at doses tolerated by the embryo. It produced histological changes in the sarcoma 180, but not in the ROS, similar to those produced by the polyfunctional alkylating agents. It is postulated that mitomycin C may act as an alkylating agent. Actinomycin D caused slight to moderate inhibition in the growth of the sarcoma 180, but the ROS was severely inhibited. Histological changes were not conspicuous in the surviving tumor cells. Mitomycin C appears to depolymerize DNA, and actinomycin D blocks DNA-dependent RNA synthesis in cells. It is postulated that the sarcoma 180 has a stable ribosomal system, so that the synthetic activity continues in the cytoplasm, although nuclear function is inhibited, whereas the ROS is more dependent on continuous RNA production for synthetic activity and survival. Thus, while the sarcoma 180 is relatively resistant to actinomycin D, both antibiotics may inhibit the ROS through its postulated dependence on RNA, either by damaging its DNA directly, or by blocking DNA-dependent RNA synthesis. Inhibition of cell growth by certain anti-cancer drugs may not depend exclusively on the rate of cellular proliferation, but may be attributed to inherent nuclear cytoplasmic relationships.

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