CSIRO Division of Human Nutrition, Glenthorne Laboratory. O'Halloran Hill, SA 5158
The foods we consume at times contain both natural and synthetic chemical compounds that are intrinsically toxic. Also present in foods, however, may be detoxifying compounds which, together with detoxification processes in our bodies, limit the damage inflicted on our metabolism. We are usually aware of the more acute responses which arise from allergens or microbial toxins, but are less aware of compounds which cause chronic diseases over time. Research at the CSIRO Division of Human Nutrition is examining the incidence and nature of mutagenic and carcinogenic events that are caused by chemicals in food and how those events may be limited or avoided by natural antimutagenic food components.
The risk to health of various food hazards has been examined objectively, based on the severity, incidence and onset of biological symptoms. The six principal categories of food hazard, ranging from greatest to least, are shown in Table 1. The ranking of these hazards however, is not linear, that of environmental contaminants and natural toxicants being about 1/1000th that of nutrient imbalance and pesticide residues and food additives being about 1/100th that of natural toxicants. This scientific perception is almost the reverse of the public's perception of risk where pesticides and food additives are seen as the greatest dangers.
Table 1. Rank Order of Food Hazards
1. Microbial contaminants
2. Nutritional imbalance (excess and deficiency)
3. Environmental contaminants
4. Natural toxicants
5. Pesticide residues
6. Food additives
Chemical compounds found naturally in foods can be toxic in a variety of ways. They can affect the nervous system, cause intestinal and liver damage, impair hormonal function or cause mutagenesis and carcinogenesis.
The glycoalkaloids -chaconine and -solanine are examples of toxic compounds found in potatoes and other members of the Solanaceae which interfere with normal function of the central nervous system and irritate the gastrointestinal tract. Acute illness and even death has followed the consumption of damaged, green or blighted potatoes. The active ingredients affect cholinesterase activity and symptoms of illness include laboured breathing, weakness, paralysis and lack of consciousness. The effects on the intestines lead to inflammation of the intestinal mucosa, ulceration and pain.
The brassica vegetables such as cauliflower, cabbage and Brussel sprout contain a complex class of sulphur containing glycosides known as the glucosinolates. These compounds can break down to form a range of products which are toxic to animals and man. They can affect growth and performance in livestock by causing liver damage, impairing normal thyroid function and interfering with other metabolic processes. Less attention has been paid to their effects in man. Some products are known to be hepatotoxic or have slight mutagenic activity while two are known to interfere with either the formation and secretion of thyroxine or with the binding of that hormone. Others, however, are thought to possess tumour suppressant activity.
Saponins, which are found amongst widely eaten legumes, act as dispersants and increase the permeability of the intestine to a wide range of toxicants such as tannins, enzyme inhibitors, phytate and oestrogenic isoflavones. This has been observed in experimental animals and clinical investigations need to be carried out in man to determine if there is synergism between saponin consumption and the biological activity of absorbed toxins.
Dietary Mutagens and Carcinogens
In relation to mammalian carcinogenesis, there are many natural compounds found in foods which have the potential to be at least mutagenic and thus pre-carcinogenic. These compounds range from actual chemicals found in some plants, such as hydrazines in mushrooms, to those produced by some mycotoxins, associated with plant products, such as the aflatoxin in peanuts. An extension of this is those toxins produced on cooking, notably the pyrolysis products of cooked meat.
Apart from the hazards of natural compounds, the residues of some chemicals used in agricultural production are of some concern if misused, as the active ingredients of some pesticides, for instance, are carcinogenic. At the recommended levels of application, the maximum residue levels (MRL) of these chemicals found in foods are such that thorough testing by industry and health authorities suggest that they are safe. There remains great public concern however, almost hysterical fear in some quarters, that foods produced in this way are harmful particularly in regard to their cancer causing effects.
The CSIRO Division of Human Nutrition is examining the mutagenic and carcinogenic effects of natural and synthetic toxicants by use of very recent genotoxic tests which are able to detect minor breakages and even recombinations of DNA genetic material which can possibly lead to cancer. Unlike some carcinogenic testing in the past where massive dosing has been used, these procedures expose experimental mice to small quantities of material over long periods.
Free superoxide radicals can arise from the detoxification of natural and synthetic toxins and to a degree from normal metabolism. Radiation and oxidants from pollutants can also be a source of these compounds which, after some modification, are able to enter the cell nucleus and damage DNA material. The body uses deoxygenating enzymes and antioxidants to limit the input of these potentially dangerous compounds and thus diets rich in antioxidants are recommended for good nutrition.
The DNA of the mammalian chromosome can be damaged in a number of ways. Single or double strand breaks can affect the DNA molecule of the chromosome and, in addition, bases can be damaged, deleted or modified by the covalent binding of mutagenic compounds (adducts). In other circumstances, strand breakage and reunion can involve exchange of material between individual chromosomes (recombination). This sort of event can lead to loss of tumour suppressor genes or activation of oncogenes which in turn may lead to cancer initiation or progression. In man there is always present a spontaneous mutation rate, but when man or animals are challenged by certain toxicants these rates increase. It is now possible to measure this increment.
In one assay, mutations can be detected by the presence of micronuclei which arise from small portions of fractured nuclei. In others, measurements in lymphocytes are made by tissue culture techniques of point mutations at x-linked loci or, alternatively, of mutations, deletions and in some cases recombinations at autosomal loci. Mutant lymphocytes are isolated by tissue culture and analysed by molecular biology techniques.
Natural Antimutagens and Anticarcinogens
Offsetting the effects of mutagenic agents are the antimutagenic/anticarcinogenic action of a diverse range of chemicals found in a variety of foods. These include the antioxidant and free radical scavengers such as tocopherol found in cereals, and vitamin A and C found in the orange and green vegetables and citrus, but many others are important also. Fibre is seen as important in that it can bind carcinogens, both internally generated (e.g. bile salts) or others consumed in the diet.
Genotoxicity and Public Health
In the past, food safety testing to a large degree has examined acute responses to foods or specific chemical compounds. The battery of tests now available to assess the genotoxicity of food components will enable us to assess the dangers which arise from the long-term consumption of mutagenic compounds. Despite the public concern over chemicals used by man, there still exists doubt about the properties of many natural compounds. In both cases, genotoxic testing should, firstly, recognise unsafe compounds and, secondly, provide scientific evidence on the protective effects of antimutagenic agents found in natural foods.