title: Modulating effects of indoles on benzo[a]pyrene-induced sister chromatid exchanges and the balance between drug-metabolizing enzymes.
abstract: The modulating effects of indole-3-carbinol (I3C) and indole-3-acetonitrile (I3A) on sister chromatid exchange (SCE) induction by benzo[a]pyrene (B[a]P) was studied. Pretreatment of cultured primary chick-embryo hepatocytes with I3C and I3A resulted in a decrease in the number of B[a]P-induced SCEs for both compounds in co-cultured V79 Chinese hamster cells. At 25 μg/ml I3C caused a twofold increase in UDP-glucuronyltransferase (UDPGT) activity. No induction of glutathione-S-transferase was found. When I3A was used (35 μg/ml), UDPGT was increased twofold whereas again no increase in glutathione-S-transferase activity was observed. When induction ratios between UDPGT activity and cytochrome P-450 content were studied, induction with both I3C and I3A resulted in ratios (UDPGT activity/cytochrome P-450 content) comparable with the control situation, whereas induction with 3-methylcholanthrene (3-MC) resulted in a considerable decrease in this ratio. Pretreatment with I3C resulted in a considerable increase in the total conversion of B[a]P into water-soluble metabolites. When the relative amounts of the individual metabolites were compared with those obtained after 3-MC pretreatment no significant differences could be observed. The results indicate that modulating effects of indoles are not directly related to induction of cytochrome P-450-associated enzymes.
authors.affiliation: Department of Toxicology, Agricultural University, De Dreyen 12, 6703 BC Wageningen, The Netherlands.
authors.forename: W M
authors.initials: WM
authors.lastname: Jongen
authors.forename: R J
authors.initials: RJ
authors.lastname: Topp
authors.forename: P J
authors.initials: PJ
authors.lastname: van Bladeren
authors.forename: J
authors.initials: J
authors.lastname: Lapre
authors.forename: K J
authors.initials: KJ
authors.lastname: Wienk
authors.forename: R
authors.initials: R
authors.lastname: Leenen