Summary
The objective of this study was to compare urinary metabolism of parent 3,3-dimethyl-1-phenyltriazene with that of its ring-substituted 1-(4-chlorophenyl)-3,3-dimethyltriazene and 1-(2,4,6-trichlorophenyl)-3,3-dimethyltriazene congeners, in an attempt to evaluate the molecular requirements for systemic carcinogenic activity. Complementary carcinogenicity assays were conducted at low equimolar dose levels using both 4- und 2,4,6-chlorinated and brominated analogues. Ring halogenation was found to prolong metabolic detoxification and to reduce carcinogenic activity.
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Abbreviations
- 4-Br-PDMT:
-
1-(4-bromophenyl)-3,3-dimethyltriazene
- 2,4,6-Br3-PDMT:
-
1-(2,4,6-tribromophenyl)-3,3-dimethyltriazene
- 4-Cl-BANEN:
-
4-(4-chlorobenzeneazo)-N-ethyl-1-naphthylamine
- 4-Cl-2-HO-BANEN:
-
4-(4-chloro-2-hydroxybenzeneazo)-N-ethyl-1-naphthylamine
- 4-Cl-PDMT:
-
1-(4-chlorophenyl)-3,3-dimethyltriazene
- 2,4,6-Cl3-BANEN:
-
4-(2,4,6-trichlorobenzeneazo)-N-ethyl-1-naphthylamine
- 2,4,6-Cl3-PDMT:
-
1-(2,4,6-trichlorophenyl)-3,3-dimethyltriazene
- DMPT:
-
3,3-dimethyl-1-phenyltriazene
- MFO:
-
mixed-function oxidase
- NEN:
-
N-ethyl-1-naphthylamine reagent
References
Druckrey H, Ivankovic S, Preussmann R (1967a) Neurotrope carcinogene Wirkung von Phenyl-dimethyl-triazen an Ratten. Naturwissenschaften 54:171
Druckrey H, Ivankovic S, Preussmann R, Brunner U (1967b) Teratogene Wirkung von 1-Phenyl-3,3-dimethyltriazen; Erzeugung von Gaumenspalten bei BD-Ratten. Experientia 23:1042–1043
Elks J, Hey DH (1943) Union of aryl nuclei. VI. Reactions with 1-aryl-3,3-dimethyltriazenes. J Chem Soc 441–445
Hunter L (1937) The azo group as a chelating group. II. The structure of the diazoamino-compounds. J Chem Soc 320–324
Johnson AW (1946) Synthesis of 2-arylfurans. J Chem Soc 895–899
Kolar GF (1984) Triazenes, In: Searle CE (ed) Chemical carcinogens, 2nd edn., American Chemical Society, Washington (in press) (ASC monograph 173)
Kolar GF, Carubelli R (1979) Urinary metabolite of 1-(2,4,6-trichlorophenyl)-3,3-dimethyltriazene with an intact diazoamino structure. Cancer Lett 7:209–214
Kolar GF, Preussmann R (1971) Validity of a linear Hammett plot for the stability of some carcinogenic 1-aryl-3,3-dimethyltriazenes in an aqueous system. Z Naturforsch [B] 26:950–953
Kolar GF, Schlesiger J (1975) Biotransformation of 1-(4-chlorophenyl)-3,3-dimethyltriazene into 3-chloro-4-hydroxyaniline. Intramolecular hydroxylation-induced chlorine migration during a catabolic degradation of a chemical carcinogen. Cancer Lett 1:43–47
Kolar GF, Schlesiger J (1976) Urinary metabolites of 3,3-dimethyl-1-phenyltriazene. Chem Biol Interact 14:301–311
Margison GP, Likhachev AJ, Kolar GF (1979) In vivo alkylation of foetal, maternal, and normal rat tissue nucleic acids by 3-methyl-1-phenyltriazene. Chem Biol Interact 25:345–353
Preussmann R, von Hodenberg A (1970) Mechanism of carcinogenesis with 1-aryl-3,3-dialkyltriazenes. II. In vivo alkylation of guanosine, RNY, and DNA with aryl-monoalkyltriazenes to form 7-alkylguanine. Biochem Pharmacol 19:1505–1508
Preussmann R, von Hodenberg A, Hengy H (1968) Mechanism of carcinogenesis with 1-aryl-3,3-dialkyltriazenes. Enzymatic dealkylation by rat liver microsomal fraction in vitro. Biochem Pharmacol 18:1–13
Preussmann R, Ivankovic S, Landschütz C, Gimmy J, Flohr E, Griesbach U (1974) Carcinogene Wirkung von 13 Aryldialkyltriazenen an BD-Ratten. Z Krebforsch 81:285–310
Rondestvedt CS, Davis SJ (1957) 1-Aryl-3,3-dialkyltriazenes as tumor inhibitors. J Organ Chem 22:200–203
Schlesiger J (1977) Stoffwechseluntersuchung ausgewählter 1-Aryl-3,3-dimethyltriazene. Dissertation, Naturwissenschaftliche Gesamtfakultät der Universität Heidelberg
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Dedicated to Professor Hermann Druckrey on the occasion of his 80th birthday
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Kolar, G.F., Habs, M. Comparative metabolism and carcinogenicity of ring-halogenated 3,3-dimethyl-1-phenyltriazenes. J Cancer Res Clin Oncol 108, 71–75 (1984). https://doi.org/10.1007/BF00390976
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DOI: https://doi.org/10.1007/BF00390976