Clinical Trial of Watercress in Detoxification of Environmental Toxicants and Carcinogens

西洋菜解毒环境毒物和致癌物的临床试验

基本信息

批准号：
9755388
负责人：
DOROTHY K HATSUKAMI
金额：
$ 61.74万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-03 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9755388
关键词：
2-butenal Acetylcysteine Acrolein Air Benzene Beverages Blood Butanones Carcinogens Cells Chemoprevention Chemopreventive Agent Cigarette Smoker Clinical Research Clinical Trials Consumption Crossover Design DNA Adducts Diet Disease Dose Drug Metabolic Detoxication Environmental Carcinogens Excretory function Exposure to Food Freeze Drying Fruit Glutathione Glutathione S-Transferase Goals Health Individual Isothiocyanates Juice Link Liquid Chromatography Malignant Neoplasms Masks Mastication Medicine Metabolic Metabolic Activation Minnesota Mus Oral Parents Phenethyl Isothiocyanate Placebos Population Powder dose form Preparation Prevalence Publishing Rattus Saliva Sampling Signal Transduction Smoker Source Standardization Testing Time Toxic Environmental Substances Transferase Urine Vegetables Watercress Weight cancer chemoprevention cancer prevention capsule design dietary constituent environmental agent environmental stressor exposed human population glutathione S-transferase M1 inhibitor/antagonist lung cancer prevention lung carcinogenesis non-smoker propylene oxide recruit tandem mass spectrometry tobacco specific lung carcinogen toxicant

项目摘要

Clinical Trial of Watercress in Detoxification of Environmental Toxicants and Carcinogens Summary In a recently completed clinical trial, we observed that 2-phenethyl isothiocyanate (PEITC) enhanced the detoxification of the environmental toxicants and carcinogens benzene, acrolein, and crotonaldehyde, as determined by increased excretion of the corresponding mercapturic acids in the urine of subjects who took 40 mg of PEITC orally per day. The significant enhancing effect was particularly strong in individuals who were null for the glutathione-S-transferase genes GST-T1, GST-M1, or both. These exciting results, which signal enhanced detoxification of commonly occurring environmental agents in subjects exposed to PEITC, led to the design of the current clinical trial of watercress, a common vegetable which is an abundant and practically unique natural dietary source of PEITC. When watercress is chewed or otherwise macerated, PEITC is released from its parent constituent gluconasturtiin. Thus, consumption of 10 grams wet weight of watercress exposes one to about 3 mg of PEITC. We hypothesize that watercress can enhance the detoxification of multiple environmental toxicants and carcinogens, thus emerging as an inexpensive and plentiful dietary constituent with potential for prevention of cancer and possibly other environmentally linked diseases. Therefore, we propose a clinical study of watercress with the following specific aims: 1. Prepare and standardize a watercress-derived beverage or capsules and appropriate placebo for the study. Two approaches will be investigated. A). Freeze-dry the watercress to obtain a powder which will be added to a mixture of fruit juices to mask the bitter watercress flavor. Subjects will drink this juice 10 min after mixing. B). Homogenize the watercress followed by freeze drying to produce a PEITC-containing powder which will be formulated into capsules. 2. Perform a clinical trial with 350 subjects to determine the effects of the watercress preparation on detoxification of environmental toxicants and carcinogens. Using a crossover design, subjects will consume the watercress beverage or capsules, or placebo, 3 times per day for 2 weeks with a 4 week washout period between watercress and placebo treatment. The target dose will be 40 mg/day of PEITC, as in our previous study. Urine, oral cells, saliva, and blood will be collected. 3. Using liquid chromatography-tandem mass spectrometry, analyze urine samples for mercapturic acids of specific toxicants (e.g. benzene, acrolein, crotonaldehyde, propylene oxide, etc.) and for mercapturic acids generally. Our hypothesis is that detoxification of these toxicants by conjugation with glutathione, as indicated by mercapturic acid levels in urine and DNA adduct levels in oral cells, will be significantly elevated compared to placebo in subjects who consumed the watercress preparation and are null for GSTM1, GSTT1, or both. The results of this study will provide a critical test of the use of watercress as a vehicle for isothiocyanates such as PEITC which can enhance detoxification of environmental toxicants and carcinogens. If the results of the trial support our hypothesis, watercress could emerge as a cheap and convenient food for cancer prevention, consistent with the concepts of “green chemoprevention and frugal medicine.”