Chapter 8

• The term cancer describes a subset of neoplastic lesions.
• A neoplasm is defined as a heritably altered, relatively autonomous growth of tissue with abnormal regulation of gene expression.
• Metastases are secondary growths of cells from the primary neoplasm.
• A carcinogen is an agent whose administration to previously untreated animals leads to a statistically significant increased incidence of neoplasms of one or more histogenetic types as compared with the incidence in appropriate untreated animals.
• Initiation requires one or more rounds of cell division for the “fixation” of the DNA damage.
• Promotion results from the selective functional enhancement of the initiated cell and its progeny by the continuous exposure to the promoting agent.
• Progression is the transition from early progeny of initiated cells to the biologically malignant cell population of the neoplasm.

Cancer is a disease of cellular mutation, proliferation, and aberrant cell growth. It ranks as one of the leading causes of death in the world. Multiple causes of cancer have been either firmly established or suggested, including infectious agents, radiation, and chemicals. Estimates suggest that 70 to 90 percent of all human cancers have a linkage to environmental, dietary, and behavioral factors.

### Definitions

Table 8–1 lists definitions of terms commonly used in discussing chemical carcinogenesis. For benign neoplasms, the tissue of origin is frequently followed by the suffix “oma”; for example, a benign fibrous neoplasm would be termed fibroma, and a benign glandular epithelium termed an adenoma.Malignant neoplasms from epithelial origin are called carcinomas, whereas those derived from mesenchymal origin are referred to as sarcoma. Thus, a malignant neoplasm of fibrous tissue would be a fibrosarcoma, whereas that derived from bone would be an osteosarcoma.

Table 8–1 Terminology.

Carcinogens may be genotoxic, meaning that they interact physically with DNA to damage or change its structure. Other carcinogens may change how DNA expresses information without modifying or directly damaging its structure, or may create a situation in a cell or tissue that makes it more susceptible to DNA damage from other sources. Chemicals belonging to this latter category are referred to as nongenotoxic carcinogens. Common features of genotoxic and nongenotoxic carcinogens are shown in Table 8–2.

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