PRINCIPLES OF TOXICOLOGY - Biology East Borneo

13.9 CANCER AND OUR ENVIRONMENT 317are mutagens and carcinogens. For example, polycyclic heterocyclic amines (PHAs) are producedwhen any amino acid is pyrolyzed (e.g., in broiling a beefsteak), and many of these are highlymutagenic. Broiling and charring foods may also increase the presence of polyaromatic hydrocarbons(PAHs).Other carcinogens are among those chemicals that are frequently found as natural or addedconstituents of the foods that make up our diet (Tables 13.16 and 13.17) or as synthetic chemicalpesticide or other residues (Table 13.18). For example, caffeic acid occurs in higher plants and hasproduced tumors in both male and female rats. The rodent carcinogen (rabbits, hamsters and mice)n-nitrosodimethylamine is found in cheeses, bacon, frankfurters, soybean oil, smoked or cured meats,fish, and some alcoholic beverages, including beer. Nitrates and nitrites occur naturally and areintroduced to foods in curing and preserving processes. It has been argued that nitrites may formcarcinogenic nitrosamines in the acid environment of the stomach by combining with amines of theaminoacids that form the protein in our diets. Thus, cooking, curing processes, applied chemicals(fertilizers, pesticides, soil or water contamination, etc.), and the selective growth of insect resistantplants are ways in which the carcinogenic load or potential of the foods we ingest may be altered.Typically, these sources outweigh the contributions by the application of synthetic pesticide by perhapsas much as 10,000-fold. So, although it is clear that naturally occurring chemicals outweigh thesynthetic chemicals we are exposed to in our diet. However, the relative contribution to the incidenceof cancer by these exposures is generally considered to be far less than is caused by the intake of excesscalories via animal fat ingestion.Finally, diets deficient in iron, selenium, and vitamin C have all been associated with increasedcancer rates. Vitamin C has been shown to inhibit the formation of certain initiating carcinogens,vitamin E appears to prevent promotion, and vitamin A appears to decrease the susceptibility ofepithelial tissue to carcinogens.Overall, the evidence indicates diet can have a profound effect on the incidence of cancer, andestimates that have diet contributing to as high as 70 percent of the total cancer incidence [perhaps asmuch as 80 percent of large bowel (colon) and breast cancers] can be found in the scientific literature.In addition, differences in diet may explain some regional geographic differences in the distributionand frequency of the cancer types observed. Like drinking alcohol and smoking, diet can also have aunknown impact on the results of epidemiologic investigations, an impact that is often inadequatelyinvestigated.TABLE 13.16 Natural Pesticides and Metabolites Found in CabbageGlucosinolates: 2-propenyl glucosinolate (sinigrin), a 3-methylthiopropyl glucosinolate, 3-methylsulfinylpropyl glucosinolate, 3-butenyl glucosinolate, 2-hydroxy-3-butenyl glucosinolate, 4-methylsulfinylbutyl glucosinolate, 4-methylsulfonylbutyl glucosinolate, benzyl glucosinolate, 2-phenylethylglucosinolate, propyl glucosinolate, butyl glucosinolateIndole glucosinolate and related indoles: 3-indolylmethyl glucosinolate (glucobrassicin), 1-methoxy-3-indolylmethyl glucosinolate (neoglucobrassicin), indole-3-carbinol, a indole-3-acetonitrile, bis(3-indolyl)methaneIsothiocyanates and goitrin: allyl isothiocyanate, a 3-methylthiopropyl isothiocyanate, 3-methylsulfinylpropylisothiocyanate, 3-butenyl isothiocyanate, 5-vinyloxazolidine-2-thione (goitrin), 4-methylthiobutylisothiocyanate, 4-methylsulfinylbutyl isothiocyanate, 4-methylsulfonylbutyl isothiocyanate, 4-pentenylisothiocyanate, benzyl isothiocyanate, phenylethyl isothiocyanateCyanides: 1-cyano-2,3-epithiopropane, 1-cyano-3,4-epithiobutane, 1-cyano-3,4-epithiopentane, threo--1-cyano-2-hydroxy-3,4-epitiobutane, erythro--1 -cyano-2-hydroxy-3,4-epithiobutane, 2-phenylpropionitrile,allyl cyanide, a 1-cyano-2-hydroxy-3-butene, 1-cyano-3-methylsulfinylpropane, 1-cyano-4-methylsulfinylbutaneTerpenes: menthol, neomenthol, isomenthol carvone aa Indicates data on mutagenicity or carcinogenicity (see Ames et al. 1990 for discussion of data); others untested.Source: Adapted from Ames et al. (1990)