Cytochemical characterization of Yoshida sarcoma cells resistant to dibromodulcitol

Two Yoshida ascites sarcoma cell populations, one of them originally sensitive and another rendered resistant to the alkylating agent dibromodulcitol (DBD), were compared for doubling time, labeling index, survival time, morphological features, cellular DNA content and modal DNA value. Cross-resistance studies were carried out on bilaterally growing solid tumours derived from the sensitive and resistant Yoshida cell populations. Glycogen-containing granules appeared in the cytoplasm of the DBD-resistant sarcoma cells; these were not present in the sensitive tumour. The growth parameters of the sensitive tumour were throughout the 10-day observation period characteristic of rapidly proliferating tumours, whereas those of the DBD-resistant tumour was characteristic of slowly proliferating systems. As compared to the mean DNA values for normal somatic cells (lymphocytes), those found for both tumours indicated that the cells were hyperdiploid aneuploid. The DNA stem line in the resistant tumour proved to be significantly smaller than that in the sensitive tumour. These results indicate that a reduction of malignancy in the Yoshida tumour is associated with a developed resistance to dibromodulcitol. The resistant tumour showing cross-resistance to dianhydrogalactitol, diacetyl-dianhydrogalactitol and to nitrogen mustard retained full sensitivity to cyclophosphamide and adriablastin (Adriamycin), and proved to be collaterally sensitive to vincristin.