Summary
A series of dimethyl aryl-triazene derivatives and related monomethyl compounds were studied for their efficacy in mediating a strong increase in immunogenicity (i.e., chemical xenogenization, CX) of murine leukemic cells following in vitro treatment. It was found that all compounds under investigation were able to induce CX. The dimethyl derivatives were able to induce CX only after metabolic activation, whereas related monomethyl compounds were active per se.
The antigenicity acquired by triazene-treated leukemic cells was very marked; intact hosts histocompatible with the parental line were able to reject up to 107 cells. Antigenic tumor cells retained their immunogenic properties even after a large number of transplant generations in the absence of the drug. This means that marked immunogenicity of triazene-treated cells is a stable and heritable characteristic.
Similar content being viewed by others
References
Bonmassar E, Bonmassar A, Vadlamudi S, Goldin A (1972) Changes of L1210 leukemic in mice treated with 5-(3–3′-dimethyl-1-triazeno)imidazole-4-carboxamide. Cancer Res 32:1446
Contessa AR, Bonmassar A, Giampietri A, Circolo A, Goldin A, Fioretti MC (1981) In vitro generation of a highly immunogenic subline of L1210 leukemia following exposure to 5-(3–3′-dimethyl-1-triazeno)imidazole-4-carboxamide. Cancer Res 41:2476
Delben F, Paoletti S, Manzini G, Nisi C (1981) Influence of serum albumins on decomposition rates of para-substituted 1-phenyl-3-methyltriazenes and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide in near-physiological conditions. J Pharm Sci 70:892
Elks J, Heyd DH (1943) Union of aryl nuclei. VI. Reactions with 1-aryl-3-3dimethyltriazenes. J Chem Soc 441
Fioretti MC (1975) Immunopharmacology of 5-(3–3′dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC). Pharmacol Res Commun 7:481
Fioretti MC, Romani L, Bonmassar A, Taramelli D (1980) Appearance of strong transplantation antigens in non-immunogenic lymphoma following drug-treatment in vivo. J Immunopharmacol 2:189
Fioretti MC, Nardelli B, Bianchi R, Nisi C, Sava G (1981) Antigenic changes of a murine lymphoma by in vivo treatment with triazene derivatives. Cancer Immunol Immunother 11:283
Fioretti MC, Bianchi R, Romani L, Bonmassar E (1983) Drug-induced immunogenic changes of murine leukemia cells: dissociation of onset of resistance and emergence of novel immunogenicity. J Natl Cancer Inst (in press)
Giampietri A, Fioretti MC, Goldin A, Bonmassar E (1980) Drug-mediated antigenic changes in murine leukemia cells: antagonistic effects of quinacrine, an antimutagenic compound. J Natl Cancer Inst 64:297
Houchens DP, Bonmassar E, Gaston MR, Kende M, Goldin A (1976) Drug-mediated immunogenic changes of virus-induced leukemia in vivo. Cancer Res 36:1347
Johnson AW (1946) Synthesis of 2-arylfurans. J Chem Soc 895
Kobayashi H (1978) Viral xenogenization of intact tumor cells. Adv Cancer Res 30:279
Kolar GF (1972) Synthesis of biologically active triazenes from isolable diazonium salts. Z Naturforsch [B] 27:1183
McLean AEM, Day PA (1974) The use of new methods to measure the effect of diet and inducers of microsomal enzyme synthesis on cytochrome P450 in liver homogenate and on metabolism of dimethylnitrosamine. Biochem Pharmacol 23:1173
Nash T (1953) The colorimetric estimation of formaldehyde by means of the hantzsch reactions. Biochem J 55:416
Riccardi C, Fioretti MC, Giampietri A, Puccetti P, Goldin A (1978) Growth and rejection patterns of murine lymphoma cells antigenically altered following drug treatment in vivo. Transplantation 25:63
Romani L, Fioretti MC, Bonmassar E (1979) In vitro generation of primary cytotoxic lymphocytes against L5178Y leukemia antigenically altered by 5-(3–3′-dimethyl-1-triazeno)-imidazole-4-carboxamide in vivo. Transplantation 28:218
Sava G, Giraldi T, Lissiani L, Nisi C (1982) Metabolism and mechanism of the antileukemic action of isomeric aryl-dimethyl-triazenes. Cancer Treat Rep 66:1751
Venger BH, Hansch C, Hatheway GH, Amrein YU (1979) Ames test of 1(x-phenyl)-3–3 dialkyltriazenes. A quantitative structure-activity study. J Med Chem 22:473
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nardelli, B., Contessa, A.R., Romani, L. et al. Immunogenic changes of murine lymphoma cells following in vitro treatment with aryl-triazene derivatives. Cancer Immunol Immunother 16, 157–161 (1984). https://doi.org/10.1007/BF00205422
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00205422