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Karl R. Grose

Bio: Karl R. Grose is an academic researcher from University of California, Berkeley. The author has contributed to research in topics: Monooxygenase & Aqueous solution. The author has an hindex of 6, co-authored 6 publications receiving 845 citations.

Papers
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Journal ArticleDOI
TL;DR: The aromatic hydrocarbon responsiveness-receptor Kd values are reported and it is shown that indolo[3,2-b]carbazole (ICZ) is produced from I3C in yields on the order of 0.01% in vitro and, after oral intubation, in vivo, and ICZ and related condensation products appear responsible for the enzyme-inducing effects of dietary I2C.
Abstract: 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. We 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. We report here the aromatic hydrocarbon responsiveness-receptor Kd values (22 nM-90 nM), determined with C57BL/6J mouse liver cytosol and the in vitro- and in vivo-molar yields (0.1-6%) of the major acid condensation products of I3C. We also show that indolo[3,2-b]carbazole (ICZ) is produced from I3C in yields on the order of 0.01% in vitro and, after oral intubation, in vivo. ICZ has a Kd of 190 pM for aromatic hydrocarbon responsiveness-receptor binding and an EC50 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 x 10(-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.

569 citations

Journal ArticleDOI
TL;DR: Evidence is presented that ICZ formation may not involve radical intermediates as is characteristic of photodynamic processes and a mechanistic rationale is presented for the formation of the identified products.
Abstract: Indole-3-carbinol [I3C, also called 3-(hydroxymethyl)indole] is a naturally occurring modulator of carcinogenesis with a biological activity that is at least partially dependent on its conversion to active substances in acidic media. We compared the identities of the major oligomeric products of I3C produced under conditions approximating those found in gastric juice with the reported identities of products of 3-substituted indoles produced under enzymatic and other nonenzymatic conditions. After a 10-min treatment in aqueous HCl solution, I3C was converted in 18% yield to a mixture of acetonitrile-soluble products, the major components of which (as determined by HPLC) were diindol-3-ylmethane (5.9%), 5,6,11,12,17,18-hexahydrocyclononal[1,2-b:4,5-b':7,8-b"]triindo le (2.0%), and [2-(indol-3-ylmethyl)indol-3-yl]indol-3-ylmethane (5.9%). Tentative assignments were made for 3,3-bis(indol-3-ylmethyl)indolenine (0.59%), a symmetrical cyclic tetramer (0.64%), and a linear tetramer (1.1%). Indolo[3,2-b]carbazole (ICZ) was formed slowly in aqueous acidic solutions in low yields (2.0 ppm) which increased to greater than 90 ppm following addition of an organic solvent [tetrahydrofuran (THF) or dimethylformamide (DMF)] to a neutralized solution. Relative yields of trimers vs dimer increased with decreasing pH and with decreasing starting concentration of I3C. Evidence is presented that ICZ formation may not involve radical intermediates as is characteristic of photodynamic processes. A mechanistic rationale is presented for the formation of the identified products.

202 citations

Journal ArticleDOI
TL;DR: Chromatographic profiles of mutagenic extracts isolated by the 4 methods suggest that the XAD-2 resin method does not recover different mutagens, but is primarily a more efficient isolation procedure.

55 citations

Journal ArticleDOI
TL;DR: Levels of ICZ significantly lower than the basal levels for conventional rats were present in feces of germfree rats, indicating that gut bacteria are important for the production ofICZ from essential dietary constituents.
Abstract: Indolo[3,2-b]carbazole (ICZ) is a potent Ah receptor agonist produced during the oligomerization of indole-3-carbinol (I3C), a breakdown product of the glucobrassicin present in food plants of the Brassica genus. Levels of ICZ present in the feces, urine, gastrointestinal tracts, and livers of rats fed on I3C- or cabbage-supplemented basal diet were 16-fold to over 100-fold higher than levels for animals on the basal diet alone. Levels of ICZ significantly lower than the basal levels for conventional rats were present in feces of germfree rats, indicating that gut bacteria are important for the production of ICZ from essential dietary constituents. Low levels of ICZ in extracts of human feces were also detected

26 citations


Cited by
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Journal ArticleDOI
TL;DR: This review covers the literature published in 2014 for marine natural products, with 1116 citations referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms.

4,649 citations

Journal ArticleDOI
TL;DR: This review addresses the complex array of glucosinolates, the precursors of isothiocyanates, present in sixteen families of dicotyledonous angiosperms including a large number of edible species including Brassica vegetables.

2,679 citations

Journal ArticleDOI
TL;DR: The role of estrogen receptors in physiology and pathology has been investigated in the past decade and it was found that there was not one but two distinct and functional estrogen receptors, now called ERα and ERβ.
Abstract: Our appreciation of the physiological functions of estrogens and the mechanisms through which estrogens bring about these functions has changed during the past decade. Just as transgenic mice were produced in which estrogen receptors had been inactivated and we thought that we were about to understand the role of estrogen receptors in physiology and pathology, it was found that there was not one but two distinct and functional estrogen receptors, now called ERα and ERβ. Transgenic mice in which each of the receptors or both the receptors are inactive have revealed a much broader role for estrogens in the body than was previously thought. This decade also saw the description of a male patient who had no functional ERα and whose continued bone growth clearly revealed an important function of estrogen in men. The importance of estrogen in both males and females was also demonstrated in the laboratory in transgenic mice in which the aromatase gene was inactivated. Finally, crystal structures of the estrogen r...

1,950 citations

Journal ArticleDOI
TL;DR: Evidence for the structural promiscuity of AhR ligand binding is described and the current state of knowledge with regards to the activation of the AhR signaling pathway by naturally occurring exogenous and endogenous ligands is discussed.
Abstract: The induction of expression of genes for xenobiotic metabolizing enzymes in response to chemical insult is an adaptive response found in most organisms. In vertebrates, the AhR is one of several chemical/ligand-dependent intracellular receptors that can stimulate gene transcription in response to xenobiotics. The ability of the AhR to bind and be activated by a range of structurally divergent chemicals suggests that the AhR contains a rather promiscuous ligand binding site. In addition to synthetic and environmental chemicals, numerous naturally occurring dietary and endogenous AhR ligands have also been identified. In this review, we describe evidence for the structural promiscuity of AhR ligand binding and discuss the current state of knowledge with regards to the activation of the AhR signaling pathway by naturally occurring exogenous and endogenous ligands.

1,716 citations

Journal ArticleDOI
TL;DR: Current research includes investigations directed towards delineating the pathways of HAH pathogenesis, ascertaining whether AHR can mediate signal transduction independently of DNA binding, understanding the mechanism of transcriptional activation, and investigating the potential roles of AHR and ARNT in development.
Abstract: The heterorneric unliga nded aryl hydrocarbon receptor complex (AHRC) con­ ta ins the aryl hydrocarbon receptor monomer (AHR). Binding of polycyclic or ha loge nated aromatic hydrocarbon (PAH and HAH) ligand causes release of AHR, which then associates with the AHR nuclear translocator protein (ARNT) to generate the heterodimeric "transformed" AHRC, AHR and ARNT belong to a novel subclass of basic helix-loop-helix -containing transcription factors. The transformed AHRC binds xenobiotic responsive elements in re­ sponsive genes and turns on their transcr iption, Certain of these genes encode enzymes involved in the metabol ic activation of PAHs to mutagenic deriva­ tives. HAHs are not genotoxic: Their pathogen icity depends on the AHRC but not on their metab olism. Current rese arch includes investigations dir ected towards delineating the pathways of HAH pathogenesis, ascer taining whether AHR can mediate signal transduction independently of DNA binding, under­ standing the mechanism of transcriptional activation, and investigating the potential roles of AHR and ARNT in development.

1,606 citations