Naturally Occurring Carcinogens

It has been estimated that the total number of known chemicals exceeds 7million, and that the great majority are naturally occurring. Although only a very small proportion (perhaps less than 0.01%) of these chemicals have been tested for carcinogenic potential in laboratory studies, a high proportion (as high as 50% in some evaluations) have been found to be positive. Therefore, even allowing for the imperfect selection and testing process, it is likely that there are a very large number of naturally occurring carcinogenic chemicals in the universe of chemicals, and therefore in the food we eat.

Naturally occurring substances identified as carcinogens in animals and humans by the range of approaches available for this purpose include inorganic compounds, organometallic compounds, and both simple and complex organic chemicals (see Table 1). These materials are present in the environment either as naturally occurring minerals or as a result of natural processes acting in the environment such as combustion, radioactive decay, or biodegradation of plant materials to oils. They are also widespread throughout the plant kingdom in both edible and nonedible plants and in many fungi and in unicellular organisms.

Inorganic Chemical Carcinogens

Many metallic elements are present as contaminants in food, being derived from a range of sources including the water used in food processing, soil residues, packaging, and cooking equipment. A number of metals and some of their salts have been shown to be carcinogenic in animals and humans, particularly to the lungs. These include arsenic,

Table 1 Examples of naturally occurring carcinogens Inorganic chemicals

Arsenic; beryllium; chromium; cobalt; cadmium; lead;

manganese; nickel Polonium; radium; uranium; radon (gas) Asbestos; silica (glassfiber); talc Organic chemicals - complex mixtures Mineral oils; shale oil; soot; wood shaving/dust Organic chemicals in higher plants

Cycasin (betel nuts); saffrole (sassafras); pyrrolizidine alkaloids (Borginaceaea, Compositae); ptaquilosides (bracken); nitrosoalkaloids (tobacco) Organic chemicals in lower order plants and microorganisms Agaratine (mushrooms); aflatoxin, ochratoxin, sterigmatocystin (Aspergillus spp. and others); mitomycin, streptozotocin, daunomycin, actinomycin (Streptomyces spp.)

beryllium, cadmium, chromium, and nickel. Little is known about the mechanism by which metals cause cancer, although evidence is emerging that some metal ions affect the fidelity of an enzyme involved in the biosynthesis of DNA resulting in abnormal DNA being produced. A number of naturally occurring radioactive elements are also carcinogenic, particularly to the lungs. These include uranium, radium, and radon gas and may act by damaging DNA directly or by increasing oxidative damage as a result of an increase in reactive radical species. In addition, some naturally occurring minerals such as asbestos, silica, and talc are known to be carcinogenic to animals and humans under some circumstances.

Organic Chemicals - Complex Natural Mixtures

The earliest association made between the development of cancer in humans and exposure to an essentially natural rather than man-made chemical was that between scrotal (skin) cancer and soot by Per-cival Pott in 1775. However, the specific chemical(s) responsible (polycyclic aromatic hydrocarbons such as benzo(a)pyrene and 7,12-dimethylbenzanthra-cene) were not identified until more than a century later. Since then, a number of other naturally occurring materials have been shown to be carcinogenic. These have included mineral oils, shale oils, and wood dust/shavings, the oils being carcinogenic to the skin and wood dust to the nasal cavity. Inadvertent ingestion of small amounts of such materials with food may be difficult to avoid.

Organic Chemicals in Higher Plants

Although the acute toxicity of many plant species has been known since written records first appeared, only comparatively recently has the carcinogenicity of plant-derived products been recognized. The list of confirmed animal carcinogens present in plants is still relatively small, and few, if any, are confirmed or suspected human carcinogens. However, developments in analytical chemistry will allow an increasingly detailed inventory to be made of chemicals in plants, which will undoubtedly result in the discovery of many more carcinogens in our foodstuffs. The recent identification of over 1000 chemicals in coffee beans, and the observation that whereas only 3% of the chemicals had been tested for carcinogenicity, nearly 70% of these tested positive, is a clear pointer to future directions. Although it can be argued that the majority of these compounds are present at very low levels in plants, and so the hazard to man from any individual compound may be small, reliable methods for assessing both hazard and risk of low-level exposure are not well developed. In addition, methods for assessing the hazard from complex mixtures of chemicals are also poorly developed, resulting in additional uncertainty in evaluating the hazard posed by natural materials. The identified chemical carcinogens in plants tend to be secondary metabolites, often present as part of the plants natural defense mechanism against predation (i.e., natural pesticides), and as such are widespread in fruit, vegetables, herbs, and spices (see Table 2).

Table 2 Some naturally occurring carcinogenic plant pesticides (a) and their sources (b)

Table 2 Some naturally occurring carcinogenic plant pesticides (a) and their sources (b)

Chemical class

Examples

Aldehyde

Crotonaldehyde; benzaldehyde;

hexanal

Hydrazine/hydrazone

N-methyl-N-formylhydrazine;

methylhydrazine; pentanal

methylformylhydrazone

Alcohol

Methylbenzyl alcohol; catechol

Ester

Ethyl acrylate; benzyl acetate

Simple heterocycles

Coumarin; hydroquinone; saffrole;

sesamol; 8-methoxypsoralen

Polyphenols

Quercetin

(b)

Generic source

Examples

Fruit

Apple; apricot; cherry; grapefruit;

lemon; melon; peach pear;

pineapple

Root vegetables

Carrot; onion; parsnip; radish; turnip

Brassica

Broccoli; Brussel sprout; cabbage

Herbs

Coriander; dill; fennel; mint; sage;

tarragon

Spices

Allspice; carroway; cardamom;

nutmeg; paprika; turmeric

One of the first classes of toxic compounds in plants to be identified were the pyrrolizidine alkaloids from the genus Senecio. Subsequently, more than 200 related compounds have been isolated from numerous families and species, many of which are potent liver toxins and liver carcinogens. Other classes of alkaloids found in the plant kingdom include derivatives of the nicotine alkaloids, such as N-nitrosonornicotine, which are present in tobacco leaves and are known to be carcinogenic to animals. Tobacco leaves also contain a range of compounds that have been shown to potentiate the carcinogenic effect of the alkaloids present.

Many other classes of carcinogenic plant products have been identified. These include glycosides of azoxy alcohols such as cycasin from betel nuts, a colon carcinogen; isoprene glycosides such as ptaqui-loside found in bracken, a liver carcinogen; and phenolic alkylbenzenes such as safrole present in many herbs and vegetables, which are also principally liver carcinogens. Other phenolic compounds including flavanoids such as quercetin, rutin and kaemferol, and tannins such as trapain and brevifolin are potent mutagens but evidence for their carcinogenicity is lacking. In fact many of these compounds have been shown to exert anticarcinogenic effects.

Organic Chemical Carcinogens in other Edible Plants and in Microorganisms

Chemical carcinogens are also found in a wide range of lower plants, such as fungi, and in microorganisms. Simple and complex hydrazines are found in many species of mushroom and have been shown to produce tumors in many tissues of experimental animals. Mycotoxins such as aflatoxin Bj and the related polynuclear compound produced by Aspergillus species are some of the most potent carcinogens known, being active at dose levels in the nanogram per kilogram range. Human exposure to such compounds occurs when cereal crops and nuts are stored in humid conditions, as they are in many parts of equatorial Africa and China. Aflatoxin B1 is one of the few established human carcinogens found in the plant kingdom. Other carcinogenic compounds produced as natural products include the antibiotics adriamycin and daunomycin and the antineoplastic agent streptozotocin isolated from microorganisms of the genus Streptomyces.

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