Abstract
Adriamycin effectively reduces the colony-forming ability of L 1210 and L 5178Y cells in culture. Its cytotoxicity is significantly greater against cells resistant to methotrexate (MTX), whether this resistance is due to an elevated level of dihydrofolate reductase or to impaired MTX transport. In all cell lines the toxicity of adriamycin increases with dose and duration of exposure. Tritiated-adriamycin enters the cells by a process that is temperature dependent, and is reduced by the presence of various metabolic inhibitors. Drug uptake occurs against a concentration gradient. Most of the drug remains associated with the trichloracetic acid-soluble fraction (approx. 70%), and the majority of drug bound to macro-molecules is associated with the DNA. A higher drug concentration is achieved in the MTX-resistant L 5178Y cells than in the MTX-sensitive L 5178Y cells, and therefore the ability of a cell to take up adriamycin may be correlated with the drug's cytotoxicity. These findings suggest that adriamycin may be a useful agent for treating neoplasms resistant to MTX or for use in combination with MTX against mixed tumour cell populations.
Published Version
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