Xenobiotic Metabolism: 01 Nutritional Effects 0 w 7.f 7 2 0 5- 8 9 1 k- b 1/ 2 0 1 0. 1 oi: d 5 | 8 9 1 6, y a M e: at D n o ati c bli u P 1 0 0 w 7.f 7 2 0 5- 8 9 1 k- b 1/ 2 0 1 0. 1 oi: d 5 | 8 9 1 6, y a M e: at D n o ati c bli u P ACS S Y M P O S I UM S E R I ES 277 Xenobiotic Metabolism: Nutritional Effects John W. Finley, EDITOR Nabisco Brands, Inc. 1 0 w0 Daniel E. Schwass, EDITOR 7.f 27 Oregon Health Sciences University 0 5- 8 9 1 k- b 1/ 2 0 1 Based on a symposium sponsored by 0. 1 oi: the Division of Agricultural and Food Chemistry d 5 | at the 187th Meeting 8 9 of the American Chemical Society, 1 y 6, St. Louis, Missouri, a M April 8-13, 1984 e: at D n o ati c bli u P American Chemical Society, Washington, D.C. 1985 Library of Congress Cataloging in Publication Data Xenobiotic metabolism. (ACS symposium series, ISSN 0097-6156; 277) "Based on a symposium sponsored by the Division of Agricultural and Food Chemistry at the 187th meeting of the American Chemical Society, St. Louis, Missouri, April 8-13, 1984." 1 0 Includes bibliographies and indexes. 0 w 7.f Co1n.g Xreesnseosb. iotics—Metabolism—Nutritional aspects— 7 2 0 I. Finley, John W., 1942- .II. Schwass, Daniel 85- E., 1951- . III. American Chemical Society. 19 Division of Agricultural and Food Chemistry. k- IV. American Chemical Society. Meeting (187th: 1984: b 1/ St. Louis, Mo.) V. Series. 2 10 QP529.X46 1985 612'.39 85-6191 0. ISBN 0-8412-0912-X 1 oi: d 5 | 8 9 1 6, y a M e: at D on Copyright © 1985 cati American Chemical Society ubli All Rights Reserved. The appearance of the code at the bottom of the first page of each P chapter in this volume indicates the copyright owner's consent that reprographic copies of the chapter may be made for personal or internal use or for the personal or internal use of specific clients. This consent is given on the condition, however, that the copier pay the stated per copy fee through the Copyright Clearance Center, Inc., 21 Congress Street, Salem, MA 01970, for copying beyond that permitted by Sections 107 or 108 of the U.S. Copyright Law. This consent does not extend to copying or transmission by any means—graphic or electronic—for any other purpose, such as for general distribution, for advertising or promotional purposes, for creating a new collective work, for resale, or for information storage and retrieval systems. The copying fee for each chapter is indicated in the code at the bottom of the first page of the chapter. The citation of trade names and/or names of manufacturers in this publication is not to be construed as an endorsement or as approval by ACS of the commercial products or services referenced herein; nor should the mere reference herein to any drawing, specification, chemical process, or other data be regarded as a license or as a conveyance of any right or permission, to the holder, reader, or any other person or corporation, to manufacture, reproduce, use, or sell any patented invention or copyrighted work that may in any way be related thereto. Registered names, trademarks, etc., used in this publication, even without specific indication thereof, are not to be considered unprotected by law. ACS Symposium Series M. Joan Comstock, Series Editor 01 Advisory Board 0 w 7.f 27 Robert Baker Robert Ory 0 5- U.S. Geological Survey USDA, Southern Regional 98 Research Center 1 bk- Martin L. Gorbaty 21/ Exxon Research and Engineering Co. Geoffrey D. Parfitt 0 Carnegie-Mellon University 1 0. 1 5 | doi: UR.oS.l aDnedp aFrt.m Henirt socfh E nergy JPahmilliepss PCe.t rRolaeunmda Cllo mpany 8 9 6, 1 Herbert D. Kaesz Charles N. Satterfield y University of California—Los Angeles Massachusetts Institute of Technology a M ate: Rudolph J. Marcus W. D. Shults D Office of Naval Research Oak Ridge National Laboratory n o blicati Vincent D. McGinniss GCehnaerralel sM So.t oTrsu Resedseaayrc h Laboratory u Battelle Columbus Laboratories P Douglas B. Walters Donald E. Moreland National Institute of USDA, Agricultural Research Service Environmental Health W. H. Norton C. Grant Willson J. T. Baker Chemical Company IBM Research Department FOREWORD The ACS SYMPOSIUM SERIES was founded in 1974 to provide a medium for publishing symposia quickly in book form. The format of the Series parallels that of the continuing ADVANCES 1 0 IN CHEMISTRY SERIES except that, in order to save time, the 0 7.fw papers are not typeset but are reproduced as they are submitted 7 by the authors in camera-ready form. Papers are reviewed under 2 0 5- the supervision of the Editors with the assistance of the Series 8 19 Advisory Board and are selected to maintain the integrity of the bk- symposia; however, verbatim reproductions of previously pub 1/ 2 lished papers are not accepted. Both reviews and reports of 0 1 0. research are acceptable, because symposia may embrace both 1 oi: types of presentation. d 5 | 8 9 1 6, y a M e: at D n o ati c bli u P PREFACE C)UR ENVIRONMENT exposes us daily to a wide variety of xenobiotics: in our food, in the air we breathe, or as a result of industrial exposure and toxic wastes. However, despite this exposure, most of us are living long, healthy lives. Certainly individual variation could account for some of the variability in resistance to disease, but other factors are undoubtedly involved. According to a growing body of evidence, diet may be extremely important in increasing resistance to chronic disease. One is tempted to speculate, or hope, that improved dietary habits could improve individual 1 resistance to chemically induced chronic disease. 0 0 pr In this volume, we have focused on how xenobiotics are metabolized in 7. 7 higher animals and how this metabolism is mediated by the nutritional status 2 0 5- of the target animal. Emphasis has been placed on the toxic, mutagenic, 8 9 carcinogenic and potentially mutagenic or carcinogenic compounds. The 1 bk- topic is a natural follow-up and expansion of "Xenobiotics in Foods and 1/ 2 Feeds" (ACS Symposium Series No. 234, Finley and Schwass, Eds.) in which 0 1 0. sources of xenobiotics were identified and discussed at length. The authors in 1 oi: this volume discuss how and why these xenobiotics are toxic and how 5 | d nutritional intervention can mediate some of the toxicities. 98 Current nutritional awareness in the western world is probably 1 6, unparalleled in the history of man. One need only look in health food stores y a and supermarkets to see the results of this awareness. Many food companies M e: now place major emphasis on the natural, pure, low-calorie, additive-free, Dat health- and fitness-oriented ingredients in their products. Nutritionists have n o established requirements for normal individuals, and additional data are cati being acquired rapidly on diets designed especially for individuals who ubli experience high stress due either to illness or life style. P This volume presents a state-of-the-art assessment of how diet can intervene and aid in the prevention of chronic disease. The editors hope this effort will stimulate further research in this important area of food biochemistry and nutrition. The authors wish to express their sincere gratitude to Miles Labora tories, Stroh Brewing Co., Nabisco Brands, Cutter Laboratories, Best Foods, General Mills, Inc., Warner Jenkinson, McCormick and Co., H. J. Heinz, and Lipton, Inc. for their generous support in helping many of the authors attend the symposium upon which this volume is based. JOHN W. FINLEY DANIEL E. SCHWASS Nabisco Brands, Inc. Oregon Health Sciences University Fair Lawn, New Jersey Portland, Oregon September 21, 1984 ix The editors would like to dedicate this volume to the memory of Morris N. Joselow whose untimely death in 1983 was a loss to all, particularly those in the area of preventative medicine. Dr. Joselow was Professor of Preventative Medicine and Community Health at the College of Medicine and Dentistry in Newark, New Jersey. One of his last published works, "Systematic Toxicity Testing for Xenobiotics in Foods," appeared in "Xenobiotics in Foods and Feeds" (ACS Symposium Series No. 234). In addition to his other duties, he was organizer and principal lecturer in the American Chemical Society Toxicology Short Course. Dr. Joselow's research interests included 1 00 environmental sciences, industrial hygiene and safety, toxicology, trace 7.pr metals, and biochemical monitoring. During his career he published more 7 2 than 100 papers. Dr. Joselow will be missed as a friend, a coworker, and a 0 85- scientist. 9 1 k- b 1/ 2 0 1 0. 1 oi: d 5 | 8 9 1 6, y a M e: at D n o ati c bli u P 1 Overview: The Influence of Nutrition on Xenobiotic Metabolism D. E. SCHWASS1,3 and J. W. FINLEY2 1U.S. Department of Agriculture, Western Regional Research Center, Berkeley, CA 94610 2Nabisco Brands, Inc., Fair Lawn, NJ 07410 In the course of living in the modern world it is inevitable 1 00 that man and animals will be exposed to compounds in the ch environment which are not essential for life or even "normal" 77. from the standpoint of the evolution of the species. The term 2 0 "xenobiotic" (from the Greek "xenos" and "bios", meaning stranger 85- to life) was coined by Mason, et al (1) to describe the myriad 9 1 of compounds including carbohydrates, lipids, proteins, k- b alkaloids, natural and synthetic drugs, flavorings, pigments, 21/ preservatives, polycyclic hydrocarbons, flavonoids, terpenoids, 0 1 etc., which may enter the organism as non-essential or 0. 1 non-functional materials. The assumption inherent in the use of oi: the term is that one is speaking relative to an organism of d 5 | reference. For example, the drug quinine is a xenobiotic 8 relative to man but not to the South American tree, Chinchona 9 y 6, 1 boafrfkic.i nXaleins,o biinot iwchs icwhh iqchui neinnteer i st hae mbaiojospr hceorne stoitfu ethnet oorfg atnhiesm are Ma not necessarily toxic. In fact, based on the Mason definition, e: non-essential amino acids could be referred to as xenobiotics. Dat For the purpose of this symposium, however, xenobiotic does not n include non-essential nutrients which occur in the diet, but will o ati be restricted to environmental compounds which are acutely toxic, blic potentially toxic requiring activation, or which exhibit long u term effects, such as mutagens, carcinogens or teratogens. In P general, the discussions in this symposium are relative to man and/or animals. It is important to remember that xenobiotics range from the inocuous (i.e. vanillin) through the chronically toxic (i.e. ethanol) to the acutely toxic (i.e. curare). Some xenobiotics, although not toxic in and of themselves, are metabolically converted to toxic substances. The metabolic conversion of xenobiotics to toxic substances can be dramatically influenced by the nutritional status of the organism. Smoking, drugs, industrial chemicals and foods, represent the major sources of exposure to xenobiotics for modern man. Because diet furnishes the most variable and continuous array of xenobiotic exposure, the emphasis of this symposium is the 3Current address: Oregon Health Sciences University, Portland, OR 97201 0097-6156/85/0277-0001 $06.00/0 © 1985 American Chemical Society 2 XENOBIOTIC METABOLISM: NUTRITIONAL EFFECTS influence of food-borne xenobiotics and how diet can mediate the metabolism of these compounds. Food borne xenobiotics can be endogenous to the foodstuff (flavinoids in tea), can result from processing and storage (lipid oxidation or non-enzymatic browning) or can be the result of deliberate addition (the antioxidant, butylated hydroxyanisole). Exposure to xenobiotics is inevitable and although the degree of exposure can be controlled, it is impossible to prevent exposure altogether. Fortunately, the healthy, well-nourished individual or animal under normal circumstances can resist long- term effects of many of these compounds by metabolizing them and excreting them as metabolites or conjugates of metabolites. A major source of exposure to xenobiotics is tobacco smoke. Cigarette smoke consists of a large variety of compounds including oxidants, free radicals, benzo-(a)-pyrene and carbon monoxide. Long term exposure to cigarette smoke entails exposure to both acutely toxic materials and chronically toxic materials. 1 00 We are all exposed to smoke in various degrees both from tobacco ch and from the environment through the burning of fuels and from 77. cooking. Exposure to industrial sources of xenobiotics can come 2 0 via the air or through exposure and absorption by the skin. 5- 8 Although major industrial exposure receives much publicity when 9 1 it occurs. This type of event usually accounts for exposure to k- b relatively few compounds over a prolonged period of time. 1/ 2 Fortunately, chemical companies have made great strides in 0 1 reducing the incidence of such exposure, although it is likely 0. 1 that some exposure will continue to occur either through oi: accidents or lack of knowledge. Industrial pollution in the form d 5 | of toxic waste should be reduced significantly in the next 98 several years as efforts continue to correct this problem. 6, 1 Exposure from toxic waste dumps is likely to continue but at y lower levels. Pharmaceutical drugs can be considered xenobiotics a M and in the western world an individual might expect to be exposed e: significantly to two-to-three dozen compounds in a lifetime under Dat normal circumstances. Frequently these exposures are over n relatively short periods of time. o ati Food represents a large and continuous exposure to a vast c bli array of xenobiotics. Xenobiotics from food can range from the Pu inocuous to the extremely dangerous. Plants frequently produce a variety of xenobiotics which subsequently are consumed by man or animals. In addition, during storage and processing of foods, (including home cooking), xenobiotics can be produced. A recent symposium (Finley and Schwass) (2) reviewed many of these sources of xenobiotics in the diet. Historically, the impact of diet on health has been a concern of man. In recent years we have seen greater emphasis on how nutrition relates to health and the prevention of chronic afflictions such as coronary heart disease, hypertension, obesity, and cancer. Consequently, several health organizations have proposed guidelines to promote better health and reduce risk