Antitumor and antimetastatic effects of benzenoid triazenes in mice bearing lewis lung carcinoma

Abstract

Summary Three parasubstiouted dimethyl-phenyltriazenes have been examined for their differential effects on primary tumor growth and lung metastasis formation in mice bearing Lewis lung carcinoma. At equitoxic dosages, the effects on the primary tumor ranged from marked depression (DM-NO2) to none (DM-CH3); those of DM-CONH2 falling inbetween. All these compounds sharply reduced the number of lung colonies, the effects of DM-CH3 being slightly more pronounced in terms of number of animals free of lung secondaries at sacrifice. In the case of DM-NO2, the depression of metastasis formation is attributed to cytotoxic effects, evident on the subcutaneous tumor. DM-CH3, on the contrary, possesses selective antimetastatic properties, since it is devoid of any effect on the growth of the primary subcutaneous implant. The activity of these compounds correlates with their half-life time of hydrolysis to aryl-diazonium cations. The three corresponding monomethyltriazenes were less active than the parent dimethyl derivatives. This suggests that microsomal oxidative N-demethylation of dimethyltriazenes to monomethyltriazenes plays a marginal role for the generation of the in vivo active species. This is further indicated by the high activity possessed by DM-COO-, another possible metabolite of DM-CONH2.