The pharmacokinetics for [14C]-BaP and metabolites will be assessed by UHLPC-Accelerator Mass Spectrometry (AMS, Lawrence Livermore National Laboratory) in plasma and urine collected over 48 hours following oral doses of 50 ng dose (5.4 nCi) alone, following 7 days' consumption of Brussels sprouts, and following 7 days' consumption of a supplement containing 3,3'-diindolylmethane (DIM).~The investigators hypothesize that pre-administration of Brussels sprouts or DIM will alter [14C]-BaP metabolism and increase the rate of elimination consistent with predictions based on a previously developed Physiologically-Based Pharmacokinetic (PBPK) model for BaP. Briefly, this hypothesis will be tested by dosing individuals with 50 ng [14C]-BaP alone and, following a 3-week washout period, ingestion of about 50 g Brussels sprouts or 300 mg of 3,3'-diindolylmethane (DIM) supplement for 7 days prior to the [14C]-BaP micro-dose. The impact of the supplement and the whole food will be assessed with respect to alterations in uptake from the GI tract, metabolism and rate of elimination. The consumption of cruciferous vegetables will be assessed at the beginning of the study by completion of a dietary questionnaire to examine typical eating patterns in the previous 3 months and by collection and extraction of blood and urine to assay for DIM by LC/ESI-MS/MS-SRM). In addition, for each phase, urine will be assayed for DIM as an estimate of crucifer or DIM supplement intake.~In preclinical and clinical studies, administration of Brussels sprouts or DIM impacts the activity of the same enzymes responsible for the phase 1 (CYP1A1 and CYP1B1) and phase 2 enzymes (GSTM1, UGT, SULT). Monitoring changes in β-estradiol metabolites will confirm the mechanism of alteration in the metabolic profile of [14C]-BaP.~Metabolite profiles and kinetics of elimination are predicted to be consistent with a BaP physiologically based pharmacokinetic (PBPK) model developed by Pacific Northwest National Laboratory (PNNL). A non-smoker, not exposed occupationally, receives 270-700 ng of BaP daily; about 95% dietary. The WHO has set an estimated safe daily lifetime (70 year/70 Kg individual, cancer endpoint) exposure to BaP of 42-350 ng. This protocol represents de minimus risk.
Evaluation of the pharmacokinetics for [14C]-benzo[a]pyrene ([14C]-BaP) and metabolites in plasma and urine over 48 hours following a 50 ng dose (5.4 nCi) alone, following 7 days' consumption of Brussels sprouts, and following 7 days' consumption of a supplement containing 3,3'-diindolylmethane (DIM).