PRINCIPLES OF TOXICOLOGY

13.9 CANCER AND OUR ENVIRONMENT 317
are mutagens and carcinogens. For example, polycyclic heterocyclic amines (PHAs) are produced
when any amino acid is pyrolyzed (e.g., in broiling a beefsteak), and many of these are highly
mutagenic. 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 added
constituents of the foods that make up our diet (Tables 13.16 and 13.17) or as synthetic chemical
pesticide or other residues (Table 13.18). For example, caffeic acid occurs in higher plants and has
produced 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 are
introduced to foods in curing and preserving processes. It has been argued that nitrites may form
carcinogenic nitrosamines in the acid environment of the stomach by combining with amines of the
aminoacids 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 resistant
plants 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 perhaps
as much as 10,000-fold. So, although it is clear that naturally occurring chemicals outweigh the
synthetic chemicals we are exposed to in our diet. However, the relative contribution to the incidence
of cancer by these exposures is generally considered to be far less than is caused by the intake of excess
calories via animal fat ingestion.
Finally, diets deficient in iron, selenium, and vitamin C have all been associated with increased
cancer 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 of
epithelial tissue to carcinogens.
Overall, the evidence indicates diet can have a profound effect on the incidence of cancer, and
estimates that have diet contributing to as high as 70 percent of the total cancer incidence [perhaps as
much 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 distribution
and frequency of the cancer types observed. Like drinking alcohol and smoking, diet can also have a
unknown impact on the results of epidemiologic investigations, an impact that is often inadequately
investigated.
TABLE 13.16 Natural Pesticides and Metabolites Found in Cabbage
Glucosinolates: 2-propenyl glucosinolate (sinigrin), a 3-methylthiopropyl glucosinolate, 3methylsulfinylpropyl
glucosinolate, 3-butenyl glucosinolate, 2-hydroxy-3-butenyl glucosinolate, 4methylsulfinylbutyl
glucosinolate, 4-methylsulfonylbutyl glucosinolate, benzyl glucosinolate, 2-phenylethyl
glucosinolate, propyl glucosinolate, butyl glucosinolate
Indole glucosinolate and related indoles: 3-indolylmethyl glucosinolate (glucobrassicin), 1-methoxy-3indolylmethyl
glucosinolate (neoglucobrassicin), indole-3-carbinol, a indole-3-acetonitrile, bis(3indolyl)methane
Isothiocyanates and goitrin: allyl isothiocyanate, a 3-methylthiopropyl isothiocyanate, 3-methylsulfinylpropyl
isothiocyanate, 3-butenyl isothiocyanate, 5-vinyloxazolidine-2-thione (goitrin), 4-methylthiobutyl
isothiocyanate, 4-methylsulfinylbutyl isothiocyanate, 4-methylsulfonylbutyl isothiocyanate, 4-pentenyl
isothiocyanate, benzyl isothiocyanate, phenylethyl isothiocyanate
Cyanides: 1-cyano-2,3-epithiopropane, 1-cyano-3,4-epithiobutane, 1-cyano-3,4-epithiopentane, threo--1cyano-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-4methylsulfinylbutane
Terpenes: menthol, neomenthol, isomenthol carvone a
a
Indicates data on mutagenicity or carcinogenicity (see Ames et al. 1990 for discussion of data); others untested.
Source: Adapted from Ames et al. (1990)