Abstract
trans-Stilbene imine (trans-1,2-diphenylaziridine) is the nitrogen analog of trans-stilbene oxide, a potent inducer of several microsomal and cytosolic xenobiotic-metabolizing enzymes. Although the acute toxicity of cis- and trans-stilbene imines prevents their application at the usual dose for trans-stilbene oxide (400 mg/kg/day), it is apparent that the imines nevertheless potently induce several xenobiotic-metabolizing enzymes in rat liver. The IP administration of trans-stilbene imine resulted in statistically significant increases in the activities of aminopyrine N-demethylase, microsomal epoxide hydrolase, glutathione transferase (toward 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene and Δ5-androstene-3,17-dione) and UDP-glucuronosyltransferase (toward testoster-one). cis-Stilbene imine was less potent in inducing these activities. Although trans-stilbene imine (total dose = 400 mg/kg) was more potent than trans-stilbene oxide (total dose = 1200 mg/kg) in inducing the activities of glutathione transferase (toward 1-chloro-2,4-dinitrobenzene) and UDP-glucuronosyltransferase (toward testosterone), both compounds belong to the class of substances which are more potent inducers of conjugating (phase II) enzymes.
Because of their structural similarity with K-region arene imines which are potent mutagens, cis-stilbene imine and trans-stilbene imine were investigated for mutagenicity (reversion of his − strains of Salmonella typhimurium). cis-Stilbene imine and trans-stilbene imine were direct mutagens in the strain TA100. This result, and the finding that acenaphthene 1,2-imine efficiently reverts various strains of Salmonella typhimurium, demonstrates that not only K-region arene imines, but also other aziridines substituted at the two carbons with aromatic moieties, are mutagenic.
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Abbreviations
- CSI:
-
cis-stilbene imine (cis-2,3-diphenylaziridine)
- CSO:
-
cis-stilbene oxide
- GSH-Px:
-
Glutathion peroxidase (activity contributed by a selenium containing enzyme, E. C.1.11.1.9, and certain GST subunits)
- GST:
-
glutathione transferase (E.C.2.5.1.18)
- MC:
-
3-methylcholanthrene
- PB:
-
phenobarbital
- TSI:
-
trans-stilbene imine (trans-2,3-diphenylaziridine)
- TSO:
-
trans-stilbene oxide
- UDP-GT:
-
uridine-5′-diphosphate glucurono-syltransferase (E.C.2.4.1.17)
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Part of Ph. D. Theses of M. A., P. R., and H. S.
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Glatt, H.R., Robertson, L.W., Arand, M. et al. Cis- and trans-1,2-diphenylaziridines: induction of xenobiotic-metabolizing enzymes in rat liver and mutagenicity in Salmonella typhimurium . Arch Toxicol 59, 242–248 (1986). https://doi.org/10.1007/BF00290545
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DOI: https://doi.org/10.1007/BF00290545