MTIC is a DNA alkylating agent, an active metabolite of dacarbazine, and an active degradation product of temozolomide.[1],[2],[3] MTIC is cytotoxic to L-cells and decreases thymidine and uridine uptake by 55 and 65%, respectively, when used at a concentration of 1 mM.[2] It is also cytotoxic to TLX5 murine lymphoma cells in a concentration-dependent manner.[3] In vivo, MTIC induces formation of mammary adenofibromas in rats when administered at a cumulative dose of 890 mg per animal over 14 weeks.[4]
Reference:
[1]. Nagasawa, H.T., Shirota, F.N., and Mizuno, N.S. The mechanism of alkylation of DNA by 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MIC), a metabolite of DIC (NSC-45388). Non-involvement of diazomethane. Chem. Biol. Interact. 8(6), 403-413 (1974).
[2]. Beal, D.D., Skibba, J.L., Whitnable, K.K., et al. Effects of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide and its metabolites on Novikoff hepatoma cells. Cancer Res. 36(8), 2827-2831 (1976).
[3]. Tsang, L.L.H., Quarterman, C.P., Gescher, A., et al. Comparison of the cytotoxicity in vitro of temozolomide and dacarbazine, prodrugs of 3-methyl-(triazen-1-yl)imidazole-4-carboxamide. Cancer Chemother. Pharmacol. 27(5), 342-346 (1991).
[4]. Beal, D.D., Skibba, J.L., Croft, W.A., et al. Carcinogenicity of the antineoplastic agent, 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide, and its metabolites in rats. J. Natl. Cancer Inst. 54(4), 951-957 (1975).