Chemical Carcinogenesis and Mutagenesis

Cancer is a common name for about 200 diseases characterized by abnormal cell growth. According to Kundson (1), the causes of cancer may be classified into the following groups: 1. genetic predisposition 2. environmental factors 3. environmental factors superimposed on genetic predisposition 4. unknown factors Typical examples of the first group are childhood cancers such as retinoblastoma (a genetically predisposed malignancy of the retina), neuroblastoma (a malignancy of the brain), and Wilms’ tumor (a malignancy of the kidney). In adults, an example is polyposis of the colon, a genetic condition that frequently leads to colon cancer. The third group is represented by xeroderma pigmentosum, a genetic condition characterized by a deficient DNA excision repair mechanism (see the discussion later in this chapter). Individuals so predisposed develop skin cancer when exposed to ultraviolet light. The variable susceptibility of the population to the carcinogenic effects of cigarette smoke may also reflect genetic predisposition. Very little can be said about the fourth group because the causes of this group of cancers are not known. Groups 2 and 3 combined (i.e., cancer attributable to environmental causes, with or without genetic predisposition) probably account for 60– 90% of all cancers (2). The environment, in this context, involves not only air, water, and soil, but also food, drink, living habits, occupational exposure, drugs, and practically all aspects of human interaction with the surroundings. This definition implies that a great majority of cancers could be prevented by avoiding exposure to potential carcinogens and by changing living habits. It is therefore not surprising that the study of chemical carcinogenesis represents a major aspect of environmental toxicology. Table 5.1 gives an overview of estimated environmentally associated cancer mortality or incidence in the United States. The data presented in this table have to be considered as rough estimates only. There are great variations in the estimates, depending on the investigators and their methods of collecting the pertinent statistics. The Office of Technology Assessment report on cancer risk offers a more in-depth treatment of this subject.