Evidence map›Paper›PMID 34035125›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2021

3,3'-Diindolylmethane Exhibits Significant Metabolism after Oral Dosing in Humans.

Monica L Vermillion Maier, Lisbeth K Siddens, Sandra L Uesugi, Jaewoo Choi, Scott W Leonard, Jamie M Pennington, Susan C Tilton, Jordan N Smith, Emily Ho, H H Sherry Chow and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 23 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Monica L Vermillion MaierDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.).
Lisbeth K SiddensDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.).
Sandra L UesugiDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.).
Jaewoo ChoiDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.).
Scott W LeonardDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.).
Jamie M PenningtonDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.).
Susan C TiltonDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.).
Jordan N SmithDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.).
Emily HoDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.).
H H Sherry ChowDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.).
Bach D NguyenDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.).
Siva K KolluriDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.).
David E WilliamsDepartment of Environmental and Molecular Toxicology (M.L.V.M., L.K.S., S.C.T., B.D.N., S.K.K., D.E.W.), the Linus Pauling Institute (M.L.V.M., S.L.U., J.C., S.W.L., J.M.P., E.H., D.E.W.), School of Biological and Population Health Sciences (E.H.), Oregon State University, Corvallis, OR; Systems Toxicology & Exposure Science, Pacific Northwest National Laboratory, Richland, WA (J.N.S.); and Cancer Center, University of Arizona, Tucson, AZ (H.H.S.C.) david.williams@oregonstate.edu.
University of Arizona · USOregon State University · USPacific Northwest National Laboratory · US

Funding

VITAMIN AP30CA023074 · NCI · UNIVERSITY OF ARIZONA · PI Teri L Bankhead · 1985 to 2026
$110.2M
Research Experience and Training Coordination CoreP42ES016465 · NIEHS · OREGON STATE UNIVERSITY · PI Robyn L Tanguay · 2009 to 2026
$52.5M
MODE OF ACTION OF ENVIRONMENTAL TOXICANTST32ES007060 · NIEHS · OREGON STATE UNIVERSITY · PI Jamie DeWitt, Siva Kumar Kolluri · 1985 to 2026
$11.6M
Zebrafish Biomedical Research Facility CoreP30ES030287 · NIEHS · OREGON STATE UNIVERSITY · PI Molly L Kile · 2020 to 2026
$9.8M
Benzo[a]pyrene Micro-dosing of Humans: A New Tool for Exposure, Risk Assessment and PreventionR01ES028600 · NIEHS · OREGON STATE UNIVERSITY · PI WILLIAMS, DAVID E · 2018 to 2022
$2.5M
NCI NIH HHS P30 CA023074NIEHS NIH HHS P30 ES030287NIEHS NIH HHS P42 ES016465NIEHS NIH HHS R01 ES028600NIEHS NIH HHS T32 ES007060
6 · The paper itself

Abstract

3,3'-Diindolylmethane (DIM), a major phytochemical derived from ingestion of cruciferous vegetables, is also a dietary supplement. In preclinical models, DIM is an effective cancer chemopreventive agent and has been studied in a number of clinical trials. Previous pharmacokinetic studies in preclinical and clinical models have not reported DIM metabolites in plasma or urine after oral dosing, and the pharmacological actions of DIM on target tissues is assumed to be solely via the parent compound. Seven subjects (6 males and 1 female) ranging from 26-65 years of age, on a cruciferous vegetable-restricted diet prior to and during the study, took 2 BioResponse DIM 150-mg capsules (45.3 mg DIM/capsule) every evening for one week with a final dose the morning of the first blood draw. A complete time course was performed with plasma and urine collected over 48 hours and analyzed by UPLC-MS/MS. In addition to parent DIM, two monohydroxylated metabolites and 1 dihydroxylated metabolite, along with their sulfate and glucuronide conjugates, were present in both plasma and urine. Results reported here are indicative of significant phase 1 and phase 2 metabolism and differ from previous pharmacokinetic studies in rodents and humans, which reported only parent DIM present after oral administration. 3-((1

Indexed as

IndolesAdministration, OralAnticarcinogenic AgentsCapsulesDietary SupplementsDrug DevelopmentDrug Elimination RoutesFemaleHumansInactivation, MetabolicMaleMiddle AgedPhytochemicals3,3'-diindolylmethaneAnticarcinogenic AgentsCapsulesindole-3-carbinolIndolesPhytochemicals

Identifiers

PMID34035125
PMCPMC8407664
OpenAlexW3164093487

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.