Abstract LB221: Randomized crossover trial evaluating detoxication of tobacco carcinogens by broccoli seed and sprout extract in heavy smokers

J. Bauman, Chiu-Hsieh Hsu, Sara M Centuori, José M. Guillén-Rodríguez, L. Garland, E. Ho, Lisa Bengtson, M. Wojtowicz, É. Szabó, H. Chow
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Abstract

Randomized crossover trial evaluating detoxication of tobacco carcinogens by broccoli seed and sprout extract in heavy smokersJulie E. Bauman, Chiu-Hsieh Hsu, Sara Centuori, Jose Guillen-Rodriguez, Linda Garland, Emily Ho, Lisa Bengtson, Malgorzata Wojtowicz, Eva Szabo, H-H Sherry ChowIntroduction: Diets high in cruciferous vegetables are associated with reduced risk of tobacco-related cancers. Crucifers are rich in the phytochemical glucoraphanin (GR), which is hydrolyzed by myrosinase to its bioactive form, sulforaphane (SF). SF upregulates the NRF2 transcription factor and downstream target genes in the antioxidant response element. As GR is concentrated in broccoli seeds relative to mature plants, broccoli seed preparations (BSP) are under development as chemopreventive agents. BSP increased detoxication of air pollutants including benzene in Qidong, China. Methods: We conducted a randomized crossover trial evaluating the detoxication of benzene and other tobacco carcinogens by the BSP Avmacol, tablets comprised of broccoli seed powder and broccoli sprout extract, in otherwise healthy smokers (≥ 20 pack-years). Each subject was treated with low and high dose BSP (70 vs. 140 GR equivalents daily for 2 weeks), separated by a 2-week washout, with randomization to low-high vs. high-low sequence. The primary endpoint was detoxication of benzene, measured by change in urinary excretion of its mercapturic acid metabolite (S-phenyl mercapturic acid, SPMA). Secondary endpoints included detoxication of the carcinogens acrolein and crotonaldehyde, and SF bioavailability assessed by urinary SF metabolites.Results: 49 subjects were randomized from Feb 2018-Nov 2019: 26 female, mean age 56.3. Treatment-related adverse events (AE) were gastrointestinal; most common were grade 1-2 bloating/cramping/abdominal pain (11; 22%), grade 1 diarrhea (11; 22%), grade 1 flatulence (10; 20%). No grade ≥ 3 AE were observed. One subject withdrew after unrelated AE. Compliance with BSP and biomarker measurements was 98%. Primary and secondary endpoints are presented in the Table. Conclusion: The BSP Avmacol was bioavailable as SF metabolites and significantly increased the acute detoxication products of benzene and acrolein in heavy smokers. Citation Format: Julie E. Bauman, Chiu-Hsieh Hsu, Sara Centuori, Jose Guillen-Rodriguez, Linda Garland, Emily Ho, Lisa Bengtson, Malgorzata Wojtowicz, Eva Szabo, H-H Sherry Chow. Randomized crossover trial evaluating detoxication of tobacco carcinogens by broccoli seed and sprout extract in heavy smokers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB221.
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摘要LB221:评价重度吸烟者西兰花籽和芽提取物对烟草致癌物解毒作用的随机交叉试验
julie E. Bauman, chu - hsieh Hsu, Sara Centuori, Jose Guillen-Rodriguez, Linda Garland, Emily Ho, Lisa Bengtson, Malgorzata Wojtowicz, Eva Szabo, H-H Sherry cho温介绍:多吃十字花科蔬菜可以降低患烟草相关癌症的风险。十字花科植物富含植物化学物质葡萄糖苷(GR),经黑芥子酶水解成其生物活性形式萝卜硫素(SF)。SF上调抗氧化反应元件中的NRF2转录因子和下游靶基因。由于相对于成熟植物,GR主要集中在西兰花种子中,因此西兰花种子制剂(BSP)作为化学预防剂正在开发中。BSP增加了中国启东包括苯在内的空气污染物的解毒。方法:我们在健康吸烟者(≥20包年)中进行了一项随机交叉试验,评估由西兰花籽粉和西兰花芽提取物组成的BSP Avmacol片对苯和其他烟草致癌物的解毒作用。每个受试者接受低剂量和高剂量BSP治疗(每天70和140 GR当量,持续2周),通过2周的洗脱期分开,随机分为低-高和高-低顺序。主要终点是苯的解毒,通过尿中苯的硫化氢代谢物(s -苯基硫化氢,SPMA)的排泄变化来测量。次要终点包括致癌物丙烯醛和巴豆醛的解毒作用,以及通过尿中SF代谢物评估SF的生物利用度。结果:49名受试者于2018年2月- 2019年11月随机纳入:女性26名,平均年龄56.3岁。治疗相关不良事件(AE)为胃肠道;最常见的是1-2级腹胀/痉挛/腹痛(11;22%), 1级腹泻(11;22%), 1级肠胃胀气(10;20%)。没有观察到≥3级AE。一名受试者因无关AE退出。BSP和生物标志物测量的依从性为98%。主要和次要终点列于表中。结论:BSP Avmacol作为SF代谢物具有生物利用性,可显著提高重度吸烟者苯和丙烯醛的急性解毒产物。引用格式:Julie E. Bauman, chu - hsieh Hsu, Sara Centuori, Jose Guillen-Rodriguez, Linda Garland, Emily Ho, Lisa Bengtson, Malgorzata Wojtowicz, Eva Szabo, H-H Sherry Chow。重度吸烟者西兰花籽和芽提取物对烟草致癌物解毒作用的随机交叉试验[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):摘要nr LB221。
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