Modulating effects of indoles on benzo[a]pyrene-induced sister chromatid exchanges and the balance between drug-metabolizing enzymes.
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.
Jongen
W M
WM
Department of Toxicology, Agricultural University, De Dreyen 12, 6703 BC Wageningen, The Netherlands.
Topp
R J
RJ
van Bladeren
P J
PJ
Lapre
J
J
Wienk
K J
KJ
Leenen
R
R