Mechanism of the antimetastatic action of N-diazoacetylglycinamide in mice bearing lewis lung carcinoma

Abstract

N-diazoacetylglycinamide (DGA) sharply reduced the formation of spontaneous pulmonary metastases in mice bearing subcutaneous Lewis lung carcinoma. At the same time, it caused no significant and parallel inhibition of primary tumor growth. The inhibition of metastasis formation, thus, appears to be due to selective antimetastatic effects, different from cytotoxicity for tumor cells. This is supported by the low effectiveness of the late treatment of mice having spontaneous metastases, and also by the absence of significant effects on the formation of artificial metastases obtained by i.v. injection of tumor cells. The lack of any cytotoxic effect for tumor cells localized in the lungs and subcutaneously was also shown by examining the effects of the treatment with DGA on the fractional incorporation of 3H -TdR in tumor cells. A proposed mechanism for the antimetastatic effects of DGA is the inhibition of tumor cell detachment from the primary implant and their access to the blood stream. This mechanism is also consistent with the fact that DGA caused the greatest reduction of spontaneous metastasis formation when administered at the same time as the peak of dissemination of tumor cells in the blood stream.