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Development of resistance to actinomycin D, daunomycin, or vincristine in Chinese hamster cells growing in vitro resulted in reversion to or retention of normal phenotypes in comparison to spontaneously transformed drug-sensitive parent populations. Sublines resistant or cross-resistant to actinomycin D showed reduced uptake of antibiotic in proportion to degree of resistance. The cells with acquired resistance were either weakly tumorigenic or nontumorigenic when tested in the cheek pouches of weanling Syrian hamsters treated with cortisone. In contrast, parent cells and several amethopterin (methotrexate)-resistant sublines produced many tumors. Antibiotic- and Vinca-alkaloid-resistant cell lines showed oriented growth patterns often associated with the behavior of normal cells in culture; antibiotic-sensitive, tumorigenic lines had morphologic characteristics of malignant cells. The altered cell membrane properties that accompanied development of resistance or cross-resistance to actinomycin D appeared to account also for the lower oncogenic potential and greater cell adhesiveness of resistant cells relative to their malignant counterparts.
Biedler et al. (Mon,) studied this question.