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

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.
• 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.