PRINCIPLES OF TOXICOLOGY - Biology East Borneo

13.11 SUMMARY 321from non-Hodgkin’s lymphoma and from melanoma are also increasing. These data were confirmedin the 1999 joint release from the CDC, NCI, and ACS.As awareness of environmental contamination and the ubiquity of synthetic chemicals arose in the1960s, specifically after the release of Rachel Carson’s Silent Spring in 1962, speculation persistedthat we were awash in a “sea of carcinogens” and that after an appropriate latency interval, a cancerepidemic would hit. As has been shown in Figure 13.1, the hypothesized epidemic of cancer has neverarrived, and considering the data indicating decreasing cancers through 1995, it would seem thatperhaps our current reductions in smoking, food consumption, and alcohol might be starting to impactthe incidence of new cancers in the United States. Considering that the stability of the cancer incidence(aside from lung cancer due primarily to smoking) occurred during a period of great industrializationin the United States, the impact of occupation and environmental pollution on cancer incidence isprobably less than what was postulated 30 years ago. That is not to say, however, that exposurereductions are not still warranted in these areas, but merely to point out that the current data indicatethat our future, with its concomitant exposure to new synthetic chemicals, is not a dire one.13.11 SUMMARYChemical-induced carcinogenesis represents a unique and complex area within toxicology. Thedifficulty in assessing the carcinogenic hazards and human risks of chemicals stems from the followingcharacteristics of chemical carcinogenesis:• It is a multistage process involving at least two distinct stages: initiation, which converts thegenetic expression of the cell from a normal to aberrant cell line; and promotion, in whichthe aberrant cell is stimulated in some fashion to grow, thereby expressing its altered state.• Since chemicals may increase cancer incidence at various stages and by different mechanisms,the term carcinogen by itself is somewhat limiting and a number of descriptive labelsare applied to the chemical carcinogens that define or describe these differences, such ascocarcinogens, initiators, promoters, and epigenetic.• Chemicals may produce or affect only a single stage or a single aspect of carcinogenesis thatleads to a number of important differences and considerations about the potential healthimpacts of chemical carcinogens. Perhaps the most important considerations are the conceptof thresholds and that qualitative differences do exist among carcinogens.• Carcinogenicity testing raises many questions about interpretations of results. Considerationssuch as mechanism (genotoxic vs. epigenetic), dose, and relevant test species,are important in determining probable human risk; thus, many additional toxicity testdata are needed to improve the extrapolation of cancer bioassay data from test speciesto humans.• A number of lifestyle-related factors influence carcinogenesis, altering the risks posed bycarcinogenic chemicals and acting to confound epidemiological evidence.Considering the complexities involved in (1) determining the mechanism of cancer causation, (2) usinganimal and human data to identify carcinogenic substances, and (3) using these data to extrapolaterisks with the aim of reducing or eliminating environmental risk factors, it should be clear to the readerthat the best approach to occupational carcinogenesis is an interdisciplinary one. As depicted in Figure13.13, identifying and reducing occupational cancer requires the interfacing of several scientificdisciplines and several kinds of health professionals:• The toxicologist is responsible for testing and identifying chemical carcinogens;through animal testing the toxicologist attempts to provide information about carcino-