Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: Comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin

Journal Article · Fri Nov 01 04:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.21.9543· OSTI ID:5822798

Bjeldanes, L F; Kim, Jinyoung; Grose, K R; Bartholomew, J C ^[1]; Bradfield, C A ^[2]

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1. Lawrence Berkeley Lab., CA (United States)
2. Northwestern Univ., Chicago, IL (United States)

Indole-3-carbinol (I3C) is a secondary plant metabolite produced in vegetables of the Brassica genus, including cabbage, cauliflower, and brussels sprouts. I3C is both an anti-initiator and a promoter of carcinogenesis. Consumption of I3C by humans and rodents can lead to marked increases in activities of cytochrome P-450-dependent monooxygenases and in a variety of phase II drug-metabolizing enzymes. The authors have reported previously that the enzyme-inducing activity of I3C is mediated through a mechanism requiring exposure of the compound to the low-pH environment of the stomach. They report here the aromatic hydrocarbon responsiveness-receptor K{sub d} values (22 nM-90 nM), determined with C57BL/6J mouse liver cytosol and the in vitro- and in vivo-molar yields of the major acid condensation products of I3C. They also show that indolo (3,2-b)carbazole (ICZ) is produced form I3C in yields on the order of 0.01% in vitro and, after oral intubation, in vivo. ICZ has a K{sub d} of 190 pM for aromatic hydrocarbon responsiveness-receptor binding and an EC{sub 50} of 269 nM for induction of cytochrome P4501A1, as measured by ethoxyresorufin O-deethylase activity in murine hepatoma Hepa 1c1c7 cells. The binding affinity of ICZ is only a factor of 3.7 {times} 10{sup {minus}2} lower than that of the highly toxic environmental contaminant and cancer promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin. ICZ and related condensation products appear responsible for the enzyme-inducing effects of dietary I3C.

• OSTI ID: 5822798
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:21; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANTINEOPLASTIC DRUGS
AROMATICS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BRASSICA
CHLORINATED AROMATIC HYDROCARBONS
CYTOCHROME OXIDASE
DAYS LIVING RADIOISOTOPES
DIET
DIOXIN
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
FOOD
HAEM DEHYDROGENASES
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
IN VITRO
IN VIVO
INDOLES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAGNOLIOPHYTA
MAGNOLIOPSIDA
MEMBRANE PROTEINS
METABOLITES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
PLANTS
PROMOTERS
PROTEINS
PYRROLES
RADIOISOTOPES
RADIORECEPTOR ASSAY
RECEPTORS
TRACER TECHNIQUES
TUMOR PROMOTERS
VEGETABLES