PHARMACOLOGICAL EFFECTS OF THERUTHENIUMCOMPLEXNAMI-A GIVEN ORALLYTO CBAMICEWITHMCaMAMMARY CARCINOMA

lIelaartmem ofBiomedical Sciences, University of Trieste, via L. Giorieri 7 Fondazione Callerio Onlus, via A. Fleming 22-31, 1-34127 Trieste, Ialy. ABSTRACT NAMI-A, imidazolium trans-imidazoledimet.hylsulfoxidetetrachlororuthenate, is a ruthenium based compounds capable of inhibitin the growth.of lung metastases of solid t.urnours in a number of experimental conditions.-The a.lm of this study was to investigate the potential use ofNAMI-A by the oral rome_to treat lung metastases ofMCamamm.aD carcinoma in the CBA mouse. Treatment or mice, carring intramuscular tumour_s .in advagced_ .stage of growth, for 11 consecutive days cause/:l a significant reduction or the weight oi lung.metastases 9ve.r the.range, of d9ses from. 150 to 6-0.0 .m.g/kg/day. N.o .sign of toxicity was observed at the histological analysis in the gut epithelium or in the kld.ney p_arenchyma, and N.AMI-A concentration in tlie kidney was more than 10-fold lower than alter intraperitone.al treatm_en.ts. NAMI-A is thus active agai.nst metastases also .by the oral route, suggesting the use orthis way to treat tumour bearing hosts for long periods. The aim of the present investigation was therefore that of examining the effects of NAMI-A given by the oral route to mice bearing the solid metastasising tumour MCa mammary carcinoma. The efficacy of NAMI-A by this route of administration should facilitate the treatment oftumour bearing hosts to cover a relatively long period oftime, as probably required for the metastatic pathology. In fact, provided that NAMI-A has repeatedly shown efficacy against metastases wih a mechanism involving the alteration of the cancer cells with host cells/tissues (13), the reduction of metastases fill their complete removal might require a long exposure of the tumour cells to the drug. In this respect, the oral route may meet this requirement, particularly if a better compliance is also proved by the host. This study therefore examines the effects of NAMI-A on lung metastasis formation in the light of the effects of the complex on primary tumour, on gut epithelium and kidney and on i:uthenium uptake by these tissues.