Assessing the effect of glucobrassicin-rich Brussels sprouts on the metabolism of deuterated phenanthrene: Developing food-based chemoprevention of tobacco-related lung cancer

Introduction: Indole-3-carbinol (I3C) and 3,3-´diindolylmethane (DIM), derived from the glucosinolate glucobrassicin, are found in cruciferous vegetables. I3C and DIM possess a potent chemopreventive effect against the development of tobacco carcinogen-induced lung tumors in mice. Polycyclic aromatic hydrocarbons (PAH) are potent lung carcinogens present in high levels in tobacco smoke. An individual’s ability to metabolically activate and/or detoxify PAH may be related to lung cancer risk from smoking. We hypothesize that I3C administered by eating a rational dose of Brussels sprouts, defined in terms of glucobrassicin concentration, can decrease the metabolic activation and/or increase detoxification of PAH, represented by the noncarcinogenic PAH [D10]Phenanthrene ([D10]Phe). Use of deuterated phenanthrene eliminates confounding by environmental phenanthrene. Metabolic activation of [D10]Phe is represented by [D10]Phenanthrene tetraol ([D10]PheT), and detoxification is represented by [D10]phenanthrol. We are conducting a clinical trial to determine whether glucobrassicin-rich Brussels sprouts can favorably modify the metabolism of the [D10]Phe. Study Design: This is a single-arm clinical trial. The primary objective is to determine the effect of a 7-day course of Brussels sprout consumption on [D10]PheT. Secondary objectives include analysis of [D10]phenanthrol and the [D10]PheT:[D10]phenanthrol ratio. Exploratory objectives include determining the correlation between 24 h urinary DIM with the reduction in [D10]PheT, and determining the effect of Brussels sprout consumption on circulating immune cell composition and activity. Forty-eight generally healthy, adult current smokers and former smokers will be enrolled. Subjects are given 1 microgram of [D10]phe, and all urine is collected for 6 hours (h) afterwards to quantify baseline levels of [D10]PheT and [D10]phenanthrol. Subjects then consume 200 micromol glucobrassicin in the form of raw Brussels sprouts (~200-300 g) once daily for 7 days. Urine is collected for 24 h after vegetable consumption on days 3 ± 1 and 6 of the feeding intervention for DIM quantification. On day 7 of the feeding intervention, a second dose of 1 microgram of [D10]phe is administered at the study center 60 minutes ± 10 minutes after vegetable consumption, followed by another 6 h urine collection. [D10]pheT and [D10]phenanthrol levels are quantified using a validated tandem mass spectrometry assay. Pre- and post-[D10]PheT levels are compared using a paired t-test after log transformation. The results will also be analyzed by GSTT1 and GSTM1 genotyping. Results: Twelve subjects have completed the study. Baseline [D10]PheT levels ranged from 48.34 to 331.05 pmol/6 h. Day 7 [D10]PheT levels ranged from 26.57 to 333.35 pmol/6 h. Percent change from baseline to Day 7 [D10]PheT ranged from a 33% decrease to an 86.5% increase (mean +/- SE of 12.8 +/- 11.6%). Conclusions: The study is ongoing and more subjects are necessary to make a definitive conclusion. Citation Format: Naomi Fujioka, Michelle To, Bruce R. Lindgren, Vincent A. Fritz, Charles Rohwer, Dorothy Hatsukami, Stephen S. Hecht. Assessing the effect of glucobrassicin-rich Brussels sprouts on the metabolism of deuterated phenanthrene: Developing food-based chemoprevention of tobacco-related lung cancer [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A41.