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

Mouse mammary carcinoma cells were exposed in 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 the 75SeM 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 formation in 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 (10 micrograms/ml ADR, 100 micrograms/ml 5-FU) inhibition of protein synthesis was significantly related to the in vivo action of the drugs in limiting formation of pulmonary tumors (P less than 0.02 using the rank difference coefficient). There was also a direct relationship between pulmonary localization of tumour cells following exposure to drugs, their ability to form tumour nodules (P less than 0.025) and the in vivo action of the drugs in inhibiting tumour formation (P less than 0.05). Thus inhibition of protein synthesis in vitro and pulmonary localization following i.v. injection may be of value in predicting the in vivo effect of cytotoxic drugs.