Inhibition of protein synthesis, pulmonary localization and pulmonary tumour formation by drug-treated tumour cells as a means of predicting their chemosensitivity

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Abstract
Mouse mammary carcinoma cells were exposedin vitro to increasing concentrations of doxorubicin hydrochloride [adriamycin (ADR)] or 5-fluorouracil (5-FU). Uptake of [75Se]selenomethionine (75SeM) in a methionine-deficient medium measured the resulting inhibition of protein synthesis by the tumour cells. This was compared with the ability of the75SeM labelled tumour cells to localize in mouse lungs and to form pulmonary tumours following intravenous (i.v.) injection into isogenic hosts. These parameters were also related to the ability of the drugs to inhibit pulmonary tumour formationin vivo when injected into mice which had received tumour cells i.v. Results from five different tumours were pooled for analysis. At the highest drug concentration (10μg/ml ADR, 100μg/ml 5-FU) inhibition of protein synthesis was significantly related to thein vivo action of the drugs in limiting formation of pulmonary tumours (Pin vivo action of the drugs in inhibiting tumour formation (Pin vitro and pulmonary localization following i.v. injection may be of value in predicting thein vivo effect of cytotoxic drugs.