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2 Naturally Occurring Carcinogens and Anticarcinogens in the Diet
Pages 35-126

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From page 35...
... EXPOSURE TO NATURALLY OCCURRING CHEMICALS Naturally occurring chemicals present in our food supply can be classifier! into the following five categories: constitutive naturally occurring substances, derived naturally occurring substances, ac quired naturally occurring substances, pass through naturally occur ring substances, ant!
From page 36...
... In contrast, there are many potentially useful foods we avoid or disregard for reasons of unawareness, aesthetics, religion, culture, or cost. All human diets that sustain life and normal activity must supply at least the minimum quantity of the essential nutrients, including calories.
From page 37...
... On average, carbohydrates supply 46% of our calories, fats supply 42%, and proteins supply 12% (Whistler and Daniel 19851. Of these component classes, proteins are the only primary gene products, i.e., the only class of components (other than DNA and the RNAs)
From page 38...
... Peptides con raining more than three, but fewer than ten amino acids, are open called oligopeptides, and those with ten or more are polypeptides. More than 400 different amino acids occur in nature (Harborne 1993)
From page 39...
... therefore foods derived from both, contain an almost unlimited variety of largely non nutrient organic com pounds often termed natural products or secondary metabolizes. In this report, natural products or secondary metabolites are cate gorized as constitutive naturally occurring chemicals.
From page 40...
... , plant pig meets (e.g., carotenes, including Vitamin A) , sterols, and rubber Protein synthesis, which combines amino acids to produce the primary gene products, proteins, including enzymes Still further complexity is found in products such as alkaloids that arise from combinations of these pathways.
From page 41...
... Fat content varies somewhat more, from 50 to 200% of the average value, in foods of both vegetable and animal origin.
From page 42...
... Alden these factors combine, the variability can be extreme: note, for example, the ascorbic acid content of paprika, for which the standard deviation (SD) is nearly equal to the mean.
From page 45...
... 8 o o ~8 o o o oo ~o o o o o _ o o o ~o o o o ~_.
From page 46...
... 46 CARCINOGENS AND ANTICARCINOGENS IN THE HUMAN DIET ber of individual substances. For example, more than 200 constitu ents have so far been isolated and identified in orange oft a simple oil (Maarse and Visscher 19891.
From page 47...
... ing the concentration of constitutive or added naturally occurring chemicals.
From page 48...
... The majority of indirect acIditives are syn thetic (see Chapter 3~. Of approximately 3,000 intentionally adcled to food, the great majority are constitutive naturally occurring chemicals.
From page 49...
... The nature and extent of the toxic effect clepends on the dose of the chemical. For practical reasons, such as those encoun tered with naturally occurring chemicals, this broad definition must often be reduced to an operational statement.
From page 50...
... Naturally occurring toxicants occur in most plants, in many microorganisms, and also in marine plants ant! animals.
From page 51...
... Very few naturally occurring chemicals have been test ed for their carcinogenic potential, and still fewer have been tested by the standard methods used to determine xenobiotics (see the section on "Dietary Plants and Cancers. Additional data, particu larly if obtained in bioassays using the maximum tolerated dose (MID)
From page 52...
... Carbohydrates are energy stores and, particularly as cellulose, structural elements in plant foods. Pro reins and their simpler relatives, pepticles, appear as enzymes, hor manes, and structural components, such as muscle.
From page 53...
... chemical ecology, are constituents that have a protec live role for the plants or animals in which they occur. This is particularly true of the constituents in the component classes called essential (or volatile)
From page 54...
... Such insistence eliminates many obviously effective repellents, skunk essence, for example. Similarly, and more significantly, the plant antioxidants such as flavone derivatives, isoflavones, catechins, coumarins, phenyl propanoicis, polyfunctional organic acicis, phosphatides, tocoph" erols, ascorbic acid, ant!
From page 55...
... Caffeic acid is a metabolic precursor of lignin, a structural polymer found in all land plants. Caffeic acid is also a component of chiorogenic acid, a phenol found widely distributed in fruits and vegetables.
From page 56...
... We simply conclude that, as far as we know now, there is a clear survival value for the plant or animal source in many of the naturally occurring toxicants found in food,
From page 57...
... using higher closes than those to which people consuming normal diets would be exposed. Dietary Plants and Cancer The ability of dietary plant extracts and constituents to induce malignant neoplasms in roclents has not been extensively stuclied, for several reasons.
From page 58...
... , very few edible plants or their crude extracts have been shown to be carcinogenic in laboratory animals. Certain plants used as herbal remedies contain carcino genie pyrrolizidine alkaloids (e.g., lasiocarpine)
From page 59...
... According to current knowledge, the limiteci number of biosyn thetic pathways in higher plants produces only a small number of constitutive naturally occurring chemicals found to be carcinogenic in animals. None of these is a potent carcinogen, comparable to the aflatoxins or the nitrosamines.
From page 60...
... Meat, eggs, milk, and other edible products from animals that consume feed contaminates! by aflatoxins are additional sources of potential exposure.
From page 61...
... Epidemiologic studies have provider! convincing evidence that dietary consumption of aflatoxins has an etiologic role in hepato carcinogenesis, and the studies indicate a synergy between chronic viral B (also C)
From page 62...
... Furthermore, barley, wheat, and pork products all appear to be human dietary sources of ochra~ toxin A MARC 1993~. Although less well stuclied, T2 toxin from Fusar~um and other species (Roclericks and Pohlanc!
From page 63...
... It is impor tent to keep in mind that these compounds are isolated from single amino acid reactions, and that the mixture of amino acids and other metabolites produces still other, more complex compounds, for instance A, Me1Q, and Me]
From page 64...
... 64 ~ Y ~ At / a; z Ed rig Z O C., is ~.= zip ~ ~o f ~, Qz ~ t ~s ~'W3
From page 65...
... .. tered for 112 weeks in the diet at 100 ppm to mate and female rats, significant increases in the incidences of neoplastic lesions were found in the liver, urinary bladder, and mammary glancis in males and in the mammary gland, hematopoietic system, and clitoral gland of females (Takahashi et al.
From page 66...
... Constitutive Naturally Occurring Carcinogens Caffeic Acid Caffeic acic] is a constitutive naturally occurring chemical fount} in higher plants.
From page 69...
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From page 70...
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From page 71...
... 1992, Li and Trush 19941; however, in their absence, caffeic acid blocks the formation of reactive oxygen species, lipid perox~cles, and nitrosamines (Toda et al. 1991; Zhou and Zheng 1991; Stich 1992; Laranjinha et al.
From page 72...
... No case reports or epidemiologic studies in humans of urethane are available, although clearly alcoholic beverages are carci nogenic to humans. On the basis of animal studies, lARC (1987)
From page 73...
... There is sufficient evidence to indicate the carcino genicity of aflatoxin in experimental animals (lARC 19931. Admin isterecl in the diet, aflatoxin B
From page 74...
... it as a Group 1 carcinogen. Derived Naturally Occurring Carcinogens PhIP (2-Amino-~-Methyt-6 Phenylimidazo[4,5-b]
From page 75...
... concludes that PhIP is possibly carcinogenic to humans and has classified it as a Group 2B carcinogen. N-Nitrosodimethylamine N nitrosodimethylamine is a derived naturally occurring carcino gen present in a variety of foocis, including cheese, soybean oil, canned fruit, various meat products and cured meats, bacon, frank furlers, ham (cooked)
From page 76...
... CURRENT STATE OF KNOWLEDGE OF HUMAN DIETARY ANTICARCINOGENS Considerable evidence suggests that the consumption of fruits ant! vegetables is important in the prevention of human cancer (NRC 1989a, Birt and Bresnick 1991, Block et al.
From page 77...
... For example, caffeic acid, chlorogenic acid, and eugenol have been observed both to increase and to inhibit the formation of neoplasias. Observations of both positive and negative effects on health have been made for numerous other compounds in foods, such as lectins, phenolic compounds, saponins, and enzyme inhibitors (Thompson 1993~.
From page 78...
... However, many of the effects of these phenolic compounds do not appear to be relatecl to this binding. It was recently proposer!
From page 79...
... It is important to note that about 70 constitutive naturally occur ring chemicals from dietary plants are reported to possess both mutagenic and antimutagenic and, in some cases antioxidant prop erties. Most of these fall under the following classes: flavonoids, phenolic acids, phenylpropanoids, coumarins, depsicles, cyctitols, isothiocyanates, catechins, simple phenols, monoterpenes, sesquiterpenes, amino acids, and anthraquinones (Farnsworth 19941.
From page 80...
... Dietary macronutrients include carbohydrates, protein, fats, and alcohol (NRC 1989a)
From page 81...
... This phenomenon, known as the caloric effect, appears to be the major effect of dietary macronutrients on carcinogenesis in experimental animals. The caloric effect, discovered early in this century, is one of the most well documenter!
From page 82...
... 1995~. Effects on cell proliferation appear to be a particularly significant means of moclu rating carcinogenesis, including effects on spontaneous tumors in rodents.
From page 83...
... . Recent studies suggest that some of the cancer prevention effects of dietary fiber may be related to the kg nan precursors anct other phytoestrogens in whole grain foods rich in fiber (Thompson 19941.
From page 84...
... Dietary fat has been extensively studied experimentally as a mod ulator in animal models of the multistage process of carcinogenesis. The data are strongest for an impact of dietary fat on events in valved in cell proliferation and gene expression (NRC 1982~.
From page 85...
... Conjugated Linoleic Acid (CLA) As linoleic acid is the only fatty acid shown unequivocally to enhance carcinogenesis, conjugated linoleic acicI (CLA)
From page 86...
... 1988~. However, few epidemiologic studies have implicated dietary protein in cancer risk
From page 87...
... EFFECT OF DIETARY MICRONUTRIENTS ON CARCINOGENESIS As noted earlier, considerable epiclemio~ogic ant! experimental evidence suggests that a number of micronutrients, including vita mins A, C, E, and selenium, contribute to cancer prevention.
From page 88...
... Much of the evidence that these micronutrients are important in cancer prevention comes from the association of fruits and vegeta bles with cancer prevention. It shoulc!
From page 89...
... 1989~. In this study of the relationship between the intake of fruits and vegetables and lung cancer risk in humans, results incli cateci a negative dose clependent relationship between dietary ,3 carotene and lung cancer risk, but no clear association for retinal, vitamin C, folic acid, iron, dietary fiber, or fruits.
From page 90...
... In addition, experimental studies with vitamin A deficient ani mats indicate an enhancement of lung cancer by 3 methyl cholanthrene and of liver and colon cancer by aflatox~n Be. While vitamin A may protect against the development of colon cancer, the presence of vitamin A deficiency inhibited N methyl N' nitro N nitrosoguanidine inducecI colon cancer in animals (Birt 1986~.
From page 91...
... reported an inverse association between con gumption of foods rich in ascorbic acid and the appearance of cer tain cancers. Since then, a comprehensive review of epiclemiologic studies has assessed the role of ascorbic acid in cancer and provided convincing evidence that ascorbic acid, an important component of fruits and vegetables, prevents cancer at a number of sites (Block 19911.
From page 92...
... and morpholine administered in the cliet, along with sodium nitrite in the drinking water, inhibited the formation of N nitrosomorpholene and liver cancer (Minxish 19831. The in hibitory role of ascorbic acid in chemically induced carcinogenesis has also been stuclied in experimental animals at other sites (e.g., skin, trachea, lung, mammary gland, colon, kidney, and urinary bladder)
From page 93...
... In con trast to the studies of vitamins A ant! C, epidemiologic studies provide less consistent support for a role of vitamin E in cancer prevention.
From page 94...
... , folic acid has been implicates} in cancer prevention. Considerable research has been conducted on the role of methyl deficiency (usually including dell ciencies of folic acicI, vitamin B 12, choline, and methionine)
From page 95...
... 19951. These observations sup port the role of folic acid in cancer prevention.
From page 96...
... 1991~. Prostate cancer risk was recently reported to be inversely associ ated with exposure to ultraviolet light and it was hypothesized that this was another cancer related to vitamin D intake (Hanchette and Schwartz 1992~.
From page 97...
... There appears to be a particularly narrow range between the intake of dietary selenium that risks deficiency and those levels at which toxicity can occur. The first investigation of the relationship between selenium and human cancer assessed the connection between forage selenium and cancer mortality (Clark et al.
From page 98...
... Breast cancer risk was not found to be related to plasma selenium in a prospective stucly on Guernsey Island] (Denmark)
From page 99...
... indicated an elevated risk of colorectal and lung cancer for inclivicluals with transferrin saturation in excess of 60% (Knekt et al.
From page 100...
... The work of Gregor Mendel in the last century provided the scientific basis for the discipline of plant breeding used so success fully in this century to improve our food plants. Animal breeders also have selected for superior characteristics in species user!
From page 101...
... 19931. Today, knowleclge of plant genetic engineering is sufficiently advanced that any charac ter that is controller} by one or only a few genes probably can be transferred to a food plant.
From page 102...
... Because genetic engi peering of ubiquitous, phytopathogenic fungi is a daunting, if not impossible task, a secondary approach shouic3 be consiclerecI. A food plant serving as host provides a source of macro and micro nutrients (sugars, amino acids, vitamins, and growth factors)
From page 103...
... SUMMARY AND CONCLUSIONS The human cliet is enormously complex; it consists of variable mixtures of dietary components. Animal studies indicate that cer lain dietary components may be carcinogenic, while others may
From page 104...
... Ongoing cancer prevention trials will help to iclenti* the importance of specific nutrients or other constituents and, in some cases, interactions between nutri ents.
From page 105...
... 1987. Aflatoxin exposure measured by urinary excretion of aflatoxin ~ guanine abduct and hepatitis B virus infection in areas with different liver cancer incidence in Kenya.
From page 106...
... 1982. A case-control dietary study of primary liver cancer risk from aflatoxin exposure.
From page 107...
... 1994. Conjugated linoleic acid is a growth factor for rats as shown by enhanced weight gain and improved feed efficiency.
From page 108...
... 1991. Aflatoxins in sera from patients with lung cancer.
From page 109...
... 1991. The role of selenium in cancer prevention.
From page 110...
... 1993b. A prospective study of dietary fat ant!
From page 111...
... dienoic derivatives of linoleic acid. Cancer Res.
From page 112...
... The Alpha Tocopherol, Beta Carotene Cancer Prevention Study Group.
From page 113...
... 1978. Chemicals with Sufficient Evidence of Carcinogenicity in Experimental Animals.
From page 114...
... 1991. Mammary cancer prevention by conjugated dienoic derivative of linoleic acid.
From page 115...
... 1985. The role of high levels of dietary fat in 7,12dimethyl benzanthracene induced mouse mammary tumorigenesis: Lack of an effect on lipid peroxidation.
From page 116...
... 1989. Vegetable consumption and lung cancer risk: A population based case control study in Hawaii.
From page 117...
... 1994. Beetling conjugated linoleic acid to animals partially overcomes catabolic responses due to enclotoxin injection.
From page 118...
... 1990. Roles of micronutrients in cancer prevention: Recent evidence from the laboratory.
From page 119...
... 1988. Dietary fat and cancer risk Evidence and research needs.
From page 120...
... liver cancer risk in Shanghai, People's Republic of China. Cancer Epidemiol.
From page 121...
... 1993. Estimating ascorbic acid requirements for cigarette smokers.
From page 122...
... 1991a. The role of infection by Opisthorchis v~verrini, hepatitis B virus, and aflatoxin exposure in the etiology of liver cancer in Thailand.
From page 123...
... 1991. Inhibition of nitrosamine formation by ascorbic acid.
From page 124...
... 1990. Dietary fat and the risk of breast cancer.
From page 125...
... pulmonary tumors in rats fed dimethyInitrosamine. Cancer Res.
From page 126...
... 1990. Diet and the risk of invasive cervical cancer among white women in the United States.


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