Modulating effects of naturally occurring indoles on SCE induction depend largely on the type of mutagen.
The modulating effects of pretreatment of cultured cells with indole-3-carbinol (I3C) and indole-3-acetonitrile (I3A) on the induction of sister-chromatid exchanges (SCEs) by mutagens from different chemical classes were investigated. Cultured primary chick embryo hepatocytes were treated for different periods with I3C (25 micrograms/ml) and with I3A (35 micrograms/ml). Treatment with I3C resulted in a 3-fold increase in ethoxyresorufine-O-deethylase (Erod) activity and a 2-fold increase in ethoxycoumarine-O-deethylase (Etco) activity. Treatment with I3A resulted in a 1.6-fold increase in Erod activity and a 2-fold increase in Etco activity. Pretreatment of cultured primary chick embryo hepatocytes with I3C resulted in a 30-45% decrease in the number of SCEs induced by benzo[a]pyrene (B(a)P) and dimethylnitrosamine (DMN) in co-cultured V79 Chinese hamster cells. No decrease in SCE induction was observed for 2-aminoanthracene (2AA) and the direct-acting alkylating agent ethyl methanesulphonate (EMS). In contrast, when dibromoethane (DBE) was tested pretreatment with I3C resulted in an increase in SCE induction. Pretreatment with I3A again resulted in a 20-40% decrease in SCE induction for B(a)P whereas no decrease was observed for DMN, 2AA and EMS. The results of this study indicate that the type of effect of indole pretreatment largely depends on the type of mutagen selected.
Jongen
W M
WM
Department of Toxicology, Agricultural University, Wageningen, The Netherlands.
Topp
R J
RJ
Wienk
K J
KJ
Homan
E C
EC
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D006224:Cricetinae; D003412:Cricetulus; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction; D007211:Indoles / Q000502:physiology*; D008099:Liver / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens; D010088:Oxidoreductases / Q000096:biosynthesis; D010105:Oxygenases / Q000096:biosynthesis; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D007211:Indoles; D009153:Mutagens; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D019363:Cytochrome P-450 CYP1A1