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Actinomycin-D-resistant in vitro mouse cell line derived from a methylcholanthrene-induced sarcoma: decrease of

J Belehradek, J L Biedler, M Thonier

    International Journal of Cancer
    |December 15, 1974
    PubMed
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    Drug-resistant EPO cells showed reduced tumor-forming ability and altered surface antigens. This study explores actinomycin D resistance in cancer cell lines and its impact on tumorigenicity and antigen expression.

    Area of Science:

    • Oncology
    • Cell Biology
    • Immunology

    Background:

    • The tumorigenic EPO clonal cell line, derived from a murine sarcoma, was used to study drug resistance.
    • Actinomycin D is a chemotherapy agent that inhibits RNA synthesis.

    Purpose of the Study:

    • To investigate the effects of actinomycin D resistance on the tumorigenic capacity and cell surface antigen expression of EPO cells.
    • To characterize the changes in cell morphology and karyotype associated with drug resistance.

    Main Methods:

    • Exposure of EPO cells to increasing concentrations of actinomycin D to develop a resistant subline (EPO/ADj).
    • Assessment of tumorigenic capacity using tumor take incidence and growth rate in syngeneic mice and hamsters.
    • Re-explantation of tumors in culture to establish EPO/ADj/T subline.

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  • Morphological and karyotypical analysis of cell lines.
  • Immunological assays including transplantation resistance and indirect immunofluorescence to detect tumor-specific antigens.

    • Main Results:

    • Actinomycin D-resistant EPO/ADj cells exhibited significantly decreased tumorigenic capacity.
    • Morphological changes were observed in resistant cells, with EPO/ADj cells being more spread and flattened.
    • Tumor-specific antigens characteristic of the parental EPO line were expressed in resistant sublines.
    • An additional surface antigen, absent in parental EPO cells, was detected in EPO/ADj and EPO/ADj/T cells.

    Conclusions:

    • Acquired resistance to actinomycin D in EPO cells is associated with a loss of tumorigenic potential.
    • Drug resistance can lead to changes in cell surface antigen expression, potentially impacting tumor immunogenicity.
    • The study identified novel surface antigens on drug-resistant cancer cells.