Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts.

Monica L Vermillion Maier, Lisbeth K Siddens, Jamie M Pennington, Sandra L Uesugi, Susan C Tilton, Emily A Vertel, Kim A Anderson, Lane G Tidwell, Ted J Ognibene, Kenneth W Turteltaub, Jordan N Smith, David E Williams

Journal: Toxicology and applied pharmacology 2023;460():116377

PMID: 36642108

Free Full Text on PubMed Central View on PubMed

Abstract

Utilizing the atto-zeptomole sensitivity of UPLC-accelerator mass spectrometry (UPLC-AMS), we previously demonstrated significant first-pass metabolism following escalating (25-250 ng) oral micro-dosing in humans of [C]-benzo[a]pyrene ([C]-BaP). The present study examines the potential for supplementation with Brussels sprouts (BS) or 3,3'-diindolylmethane (DIM) to alter plasma levels of [C]-BaP and metabolites over a 48-h period following micro-dosing with 50 ng (5.4 nCi) [C]-BaP. Volunteers were dosed with [C]-BaP following fourteen days on a cruciferous vegetable restricted diet, or the same diet supplemented for seven days with 50 g of BS or 300 mg of BR-DIM® prior to dosing. BS or DIM reduced total [C] recovered from plasma by 56-67% relative to non-intervention. Dietary supplementation with DIM markedly increased T and reduced C for [C]-BaP indicative of slower absorption. Both dietary treatments significantly reduced C values of four downstream BaP metabolites, consistent with delaying BaP absorption. Dietary treatments also appeared to reduce the T and the plasma AUC() for Unknown Metabolite C, indicating some effect in accelerating clearance of this metabolite. Toxicokinetic constants for other metabolites followed the pattern for [C]-BaP (metabolite profiles remained relatively consistent) and non-compartmental analysis did not indicate other significant alterations. Significant amounts of metabolites in plasma were at the bay region of [C]-BaP irrespective of treatment. Although the number of subjects and large interindividual variation are limitations of this study, it represents the first human trial showing dietary intervention altering toxicokinetics of a defined dose of a known human carcinogen.

Address: Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA; Department of Environmental and Molecular Toxicology, ALS 1007, Oregon State University, Corvallis, OR 97331, USA. Electronic address: [email protected].; Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA. Electronic address: [email protected].; Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA. Electronic address: [email protected].; Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. Electronic address: [email protected].; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA; NIEHS Superfund Research Program, Oregon State University, Corvallis, OR 97331, USA. Electronic address: [email protected].; Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA. Electronic address: [email protected].; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA; NIEHS Superfund Research Program, Oregon State University, Corvallis, OR 97331, USA. Electronic address: [email protected].; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA. Electronic address: [email protected].; Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. Electronic address: [email protected].; Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA; Biology and Biotechnology Research Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. Electronic address: [email protected].; NIEHS Superfund Research Program, Oregon State University, Corvallis, OR 97331, USA; Chemical Biology and Exposure Science, Pacific Northwest National Laboratory, Richland, WA 99354, USA. Electronic address: [email protected].; Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA; NIEHS Superfund Research Program, Oregon State University, Corvallis, OR 97331, USA. Electronic address: [email protected].

DOI: 10.1016/j.taap.2023.116377

Link outs

Free resources

Full Text Sources:

Subscription / membership required

Full Text Sources:

MeSH Terms: Humans, Benzo(a)pyrene, Carcinogens, Dietary Supplements, Toxicokinetics