Natural anticarcinogens, carcinogens, and changing patterns in cancer: some speculation

Over the past two decades, marked shifts have occurred in cancer mortality in the United States, the United Kingdom, and the Federal Republic of Germany. Stomach cancer mortality has declined sharply, while brain cancer and multiple myeloma increased nearly twofold for persons ages 75 to 84. Total cancer incidence in the United States, excluding lung cancer, has risen 27% since 1950, adjusted to the aging of the population. The origins of these trends are not known. The diet in the developed countries includes a number of naturally occurring, powerful anticarcinogens and carcinogens. To evaluate the role of these substances in the prevention and causation of human cancer, this paper reviews existing toxicologic and epidemiologic data. These data indicate that naturally occurring substances in food influence cancer initiation, promotion, progression, and demotion by a number of mechanisms, including (1) covalent binding to DNA of naturally occurring anticarcinogenic compounds to block the initiation of carcinogenesis; (2) induction of biotransforming enzymes such as cytochrome P450 and mixed-function oxidase (MFO) which can reduce carcinogenicity; (3) inhibition of tumor promotion by compounds such as retinol, tocopherol, and organosulfates found in garlic, onions, fruits, and vegetables; and (4) physical alteration of carcinogens by food constituents or by food preparation and handling so as to alter carcinogenicity. Systems have been proposed for estimating the relative ranking for humans of individually tested, experimental carcinogens, including some constituents of food. While qualitatively useful, such systems as the HERP Index do not take into account important interactions among naturally occurring and synthetic constituents in foods, nor do they permit examination of the possible role of evolved resistance. Common mixtures in food must be tested for carcinogenicity in human tissue cultures and in long-term rodent bioassays. Such studies need to examine whether the action of synthetic organic carcinogens may be inhibited by potent naturally occurring anticarcinogens.