Benzo[$\mathcal{a}$]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts

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

doi:10.1016/j.taap.2023.116377

Benzo[$$\mathcal{a}$$]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts

Journal Article · Fri Jan 13 00:00:00 EST 2023 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2023.116377· OSTI ID:1922417

Vermillion Maier, Monica L. ^[1]; Siddens, Lisbeth K. ^[1]; Pennington, Jamie M. ^[1]; Uesugi, Sandra L. ^[1]; Tilton, Susan C. ^[1]; Vertel, Emily A. ^[1]; Anderson, Kim A. ^[1]; Tidwell, Lane G. ^[1]; Ognibene, Ted J. ^[2]; Turteltaub, Kenneth W. ^[2]; Smith, Jordan N. ^[3]; Williams, David E. ^[1]

Oregon State Univ., Corvallis, OR (United States)
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Oregon State Univ., Corvallis, OR (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

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 [¹⁴C]-benzo[a]pyrene ([¹⁴C]-BaP). The present study examines the potential for supplementation with Brussels sprouts (BS) or 3,3' -diindolylmethane (DIM) to alter plasma levels of [¹⁴C]-BaP and metabolites over a 48-h period following micro-dosing with 50 ng (5.4 nCi) [¹⁴C]-BaP. Volunteers were dosed with [¹⁴C]-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 [¹⁴C] recovered from plasma by 56–67% relative to nonintervention. Dietary supplementation with DIM markedly increased T_max and reduced C_max for [¹⁴C]-BaP indicative of slower absorption. Further, both dietary treatments significantly reduced C_max values of four downstream BaP metabolites, consistent with delaying BaP absorption. Dietary treatments also appeared to reduce the T_1/2 and the plasma AUC(_0,$$\infty$$) for Unknown Metabolite C, indicating some effect in accelerating clearance of this metabolite. Toxicokinetic constants for other metabolites followed the pattern for [¹⁴C]-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 [¹⁴C]-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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE; USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC05-76RL01830; AC52-07NA27344

OSTI ID:: 1922417

Alternate ID(s):: OSTI ID: 2008147
OSTI ID: 1910290

Report Number(s):: LLNL--JRNL-855317; PNNL-SA--181291

Journal Information:: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 460; ISSN 0041-008X

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Benzo[$$\mathcal{a}$$]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts

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