A co-cultivation system as a model for in vitro studies of modulating effects of naturally occurring indoles on the genotoxicity of model compounds

Toxicology in Vitro : an International Journal Published in Association with BIBRA
W M JongenE J Brink

Abstract

An in vitro model system, consisting of primary chick embryo hepatocytes as the metabolizing system co-cultured with V79 Chinese hamster cells as the target cells for the SCE assay, was used to study the modulating effects of naturally occurring indoles on the genotoxicity of benzo[a]pyrene (B[a]P) and N-nitrosodimethylamine (NDMA). At 25 mug/ml, indole-3-carbinol (I3C) induced ethoxyresorufin-O-deethylase (ERROD) activity 3.9-fold and ethoxycoumarin-O-deethylase (ETCO) activity 2-fold. Indole-3-acetonitrile (I3A; 35 mug/ml) induced ERROD activity 1.6-fold and ETCO activity 2-fold. Pretreatment with I3C resulted in a 20-40% decrease in genotoxicity for both B[a]P and NDMA. Pretreatment with I3A resulted in a similar decrease in genotoxicity for B[a]P, whereas no decrease was observed for NDMA. When a microsomal fraction prepared from I3C-pretreated hepatocytes was used, no decrease in B[a]P-induced genotoxicity was found; in contrast, use of an S-9 fraction prepared from the same cells resulted in a 45% decrease. Exposure of cells to B[a]P after pretreatment with I3C for suboptimal times also resulted in a significant decrease in genotoxic activity. The data indicate that the protective effects of pretreatment with the indoles,...Continue Reading

References

Jun 1, 1985·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·W M JongenJ C van der Hoeven
Feb 1, 1982·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·J N BoydG S Stoewsand
Aug 1, 1983·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·S Hendrich, L F Bjeldanes
Apr 1, 1984·Mutation Research·J C van der HoevenF M Debets
Apr 1, 1981·Mutation Research·W M JongenJ H Koeman

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Citations

Jan 1, 1989·Toxicology in Vitro : an International Journal Published in Association with BIBRA·W M JongenR Leenen
Mar 19, 1997·Cancer Letters·M A van Boekel, W M Jongen
Mar 1, 1996·The Proceedings of the Nutrition Society·W M Jongen
Nov 29, 2007·Human & Experimental Toxicology·Jaap C Hanekamp, Aalt Bast

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