Environmental Carcinogenesis and Cancers* W. C. HuEPER (National Cancer Institute, Bethesda, Md.) I. THE NATURE AND SCOPE OF ENVIRON- dustrial effluents and in automobile exhaust as MENTAL CANCER HAZARDS well as associated with cigarette smoking. Almost ~00 years have passed since the first 3. The demonstration of a considerable and ris- environmental carcinogen, coal soot, was recog- ing number of carcinogenic chemicals used as in- nized as the cause of cancer of the human skin. tentional and nonintentional food additives and The environmental carcinogenic spectrum com- produced in the food because of certain processing posed of accepted, suspected, and potentially car- procedures as well as employed as ingredients, or cinogenic agents present in the natural and artifi- present as impurities in drugs, cosmetics, economic cial human environment has grown considerably poisons, and other consumer goods. during the intervening years. Despite the impres- It is significant that, in response to these devel- sive increase therefrom, resulting in the number, opments, federal, state and municipal legislatures diversity, and spread of environmental cancer and public health authorities have enacted laws or hazards among the general and especially the in- issued regulations during the last decade providing dustrially employed and urban populations and increased protection of the general public against despite the ready availability of an abundant cancer hazards resulting from an environmental amount of reliable facts and observations on the dissemination of carcinogens in foods, drugs, and causation of human cancers by environmental cosmetics and in effluents of industrial plants and agents, governmental, private, and professional automobiles. For the first time during the modern parties directly concerned with the protection and industrial era, protective legal measures which, up maintenance of human health have displayed until to that time, had been applied to occupational recently an astounding indifference and aloofness cancer hazards only were extended to those of gen- toward this important aspect of the general cancer eral environmental nature. Formal recognition was problem. A partial awakening from this general given thereby to the long neglected fact that many state of lethargy has, however, occurred during the of the known environmental carcinogens initially last decade because of the impact produced by the encountered in certain occupational activities are strong reaction of the general public to widely dis- subsequently being introduced into the general seminated information relative to the increasing human environment as pollutants of the air, water, and probably dangerous contamination of the hu- and soil and as constituents and impurities of man environment and of many products of daily many consumer goods, and are creating through consumption with carcinogenic agents. this mechanism a serious public health problem. This rising concern with mainly industry-relat- While mankind has had contact, during the ed environmental cancer hazard was aroused by greater part of its existence on earth, with a num- three recent developments: ber of natural as well as man-made environmental 1. The growing contamination of air, water, carcinogens such as sunlight, ionizing radiations, and soil as well as of foodstuffs with radioactive arsenicals, infections with Schistosoma hematobi- matter from activities in the nuclear energy field. um, soot, and possibly tobacco products, the hu- ~. The increasing pollution of the inhaled air man race has had a chance through the thousands with various chemical carcinogens contained in in- of years of exposure to develop against these car- * Based upon a paper presented at a Symposium on the cinogens some defense mechanisms in the form of Current Status of Cancer Research at a meeting of the Ameri- detoxication and chemoimmunity reactions and can Association for Cancer Research in Atlantic City on other protective biologic responses, such as in- April 8, 1961. creased pigmentation. Mankind, on the other Received for publication March 17, 1961. hand, has not had any opportunities for develop- 84~ Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1961 American Association for Cancer Research. HuEeER~Environmental Carcinogenesis 843 ing any reactions of biologic adaptation to the en- tion products, such as tubercles and gummas, and vironmental carcinogens of the modern industrial then to use such information for devising chemical era, because of their introduction during a period means against some of the biologic mechanisms or of only a few decades. The protection of modern some special constituents found in such circum- mankind against the growing number of these scribed anatomic reaction products, or for develop- man-made chemical and physical carcinogens ing diagnostic tests for infectious granulomas, ir- must rely, therefore, entirely on methods and respective of their specific etiology. measures artificially devised. Because of the past failure to obtain, by the ap- The extent to which the contamination of the plication of this biologic concept of cancer, any re- human environment with new artificial, man-made liable specific diagnostic test for cancer and any physical and chemical carcinogens has progressed effective chemotherapeutic agent against cancer- during the past century is strikingly illustrated by ous tissue, one is left wondering whether it is not the long list of known, suspected, and potential appropriate and timely to put to work in this re- human carcinogens, the various routes of contact search the many facts and observations on envi- with them, the numerous opportunities of expo- ronmental carcinogenesis and cancers, and to re- sure to them, the different sites of cancers pro- turn to those scientific principles which brought duced by them, and the progressive march of occu- success to the control of infectious diseases. The pational cancers through the individual countries advisability to explore more fully the potentialities subsequent to the development of an industrial TABLE 1 economy (Table 1) (4, 17, ~, 56, 68-70, 7~, 73). The presently known spectrum of recognized, sus- TIMETABLE OF THE DISCOVERY OF AROMATIC AMINE pected, and potential human carcinogens exhibits CANCERS OF TIIE BLADDER IN DIFFERENT a remarkable degree of diversity and complexity COUNTRIES of its component members. It is comprised of sev- eral parasitic and viral organisms, of a growing Country Discoverer Year number of carbon and silicon macromolecular Germany Rehn 1895 polymerized chemicals, of various specific organic Switzerland Schedler 1905 aromatic and aliphatic chemicals, of several metals Great Britain ROSS 1918 Russia Rosenbaum & Gottlieb 1926 and minerals, and of various nonionizing and ion- Austria Schtiller 1932 izing radiations which exert an actinochemical United States Ferguson el al. 1934 Italy di Maio 1936 action on the chemical constituents of tissues being .Japan Nagayo & Kinosita 1940 exposed to these radiations. France Billiard-Duchesne 1946 It has often been argued in the past that, be- cause of the multitude and diversity of carcino- genic agents, cancers do not represent an anatomic of the etiology-specific concept of cancer for its reaction product of tissues to a specific carcino- diagnosis, prophylaxis, and treatment is suggested genic agent which retains in its biologic respon- by the many similarities existing between the siveness and properties a direct relation to the spectra of environmental carcinogens and of specific causal agent. The prevailing concept con- pathogenic microorganisms. siders cancers as biologic manifestations which de- Both major systems of disease-producing agents velop in response to carcinogenic stimuli and include a wide range of different component mem- which assume, once produced, complete biologic bers varying markedly in their degree of potency independence from the causal agent, thereby be- or virulence among each other--i.e., from produc- coming disease entities per se. Almost the entire ing a 100 per cent attack rate in the population to modern diagnostic and chemotherapeutic research the risk of affecting only a fraction of it or the ex- in cancer control is based on this concept. This ceptional individual. There exist, moreover, definite approach is rather surprising and unique in the and epidemiologically important differences in annals of medicine and contrasts sharply with the their pathogenicity or their carcinogenicity, re- efforts made in the past for controlling infectious spectively, for different species, strains, races, and diseases. These efforts were directed toward influ- individuals of the same race or strain. encing the causative agents and their toxic prod- This observation on the significance of the host ucts by biologic and chemical means. It has not reaction for the occurrence of a carcinogenic re- occurred to investigators engaged in such tasks to sponse has led to the contention that the host rela- attempt the development of curative agents tionship might be more important in this respect against these diseases by first obtaining detailed than the carcinogen proper and that, therefore, a biochemical information on their anatomic reae- control of cancer hazards might be achieved by Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1961 American Association for Cancer Research. 844 Cancer Research Vol. ~1, August 1961 modifying in the right direction the constitution- determining the