In vitro testing and the carcinogenic potential of several nitrosated indole compounds |
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Authors: | Henrika G M Tiedink Laura H J De Haan Wim M F Jongen Jan H Koeman |
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Institution: | (1) Department of Toxicology, Agricultural University, Wageningen, The Netherlands;(2) Agrotechnological Research Institute, Wageningen, The Netherlands;(3) Agrotechnological Research Institute, P.O. Box 17, AA Wageningen, The Netherlands |
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Abstract: | 4-chloro-methoxyindole is a naturally occurring compound in Vicia faba which can easily react with nitrite to form a N-nitroso compound. In this in vitro study, the potential genotoxic effects of nitrosated 4-chloro-6-methoxyindole and its structural analogue 4-chloroindole were evaluated for the first time by using both Salmonella and Chinese hamster V79 cells. Additionally, the inhibition of gap junctional intercellular communication in V79 cells by these compounds was determined; this is a validated parameter for tumor-promoting activity. Most assays were also performed with nitrosated indole-3-acetonitrile, a naturally occurring compound in brassicas. Both nitrosated chloroindoles were highly mutagenic to Salmonella typhimurium TA100 without the need of exogenous metabolic activation and were potent inducers of Sister Chromatid Exchanges. Nitrosated indole-3-acetonitrile generated the same effects, although at much higher concentrations. Equivocal results were obtained for the nitrosated chloroindoles in a forward mutation assay using the hypoxanthine guaninephosphoribosyltransferase locus. All nitrosated indole compounds significantly inhibited gap junctional intercellular communication. These results indicate that nitrosated chloroindoles and nitrosated indole-3-acetonitrile should be considered as mutagens and agents with potential tumor-promoting capacity.Abbreviations BrdU
5-bromo-2-deoxyuridine
- 4Cl
4-chloroindole
- 4C6MI
4-chloro-6-methoxy-indole
- DMSO
dimethyl sulfoxide
- EBSS
Earle's balanced salt solution
- EMS
ethyl methanesulfonate
- GJIC
gap junctional intercellular communication
- HBSS
Hanks balanced salt solution
- HGPRT
hypoxanthine guaninephosphoribosyl transferase
- I3A
indole-3-acetonitrile
- MNNG
1-methyl-1-nitroso-3-nitroguanidine
- NOC
N-nitroso compounds
- NQO
4-nitroquinolone-N-oxide
- SCE
sister chromatid exchange
- 6TG
6-thioguanine
- TPA
12-O-tetradecanoylphorbol-13-acetate |
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Keywords: | chloroindoles precursors N-nitroso compounds Vicia faba mutagenicity tumor prometer capacity |
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