PRINCIPLES OF TOXICOLOGY - Biology East Borneo

314 CHEMICAL CARCINOGENESISFigure 13.12 Cancer incidence rates for U.S. males, annual trends. (From Cancer Facts and Figures—1999,American Cancer Society.)Lung cancer mortality rates are about 23 times higher for current male smokers and 13 timeshigher for current female smokers compared to lifelong never-smokers. In addition to beingresponsible for 87 percent of lung cancers, smoking is also associated with cancers of the mouth,pharynx, larynx, esophagus, pancreas, uterine cervix, kidney, and bladder. Smoking accountsfor at least 30 percent of all cancer deaths, is a major cause of heart disease, and is associatedwith conditions ranging from colds and gastric ulcers to chronic bronchitis, emphysema, andcerebrovascular disease.The data surrounding smoking is particularly distressing for persons who might be occupationallyexposed to other substances as well. Asbestos-exposed workers who smoke reportedly contract lungcancer at a rate that is 60 times that of persons not exposed to either substance. Other risk factors forlung cancer may include exposure to arsenic, some organic chemicals, radon, radiation exposure fromoccupational, medical, and environmental sources. Smokers who incur such exposures should be awareof the increased risks they face compared to their nonsmoking co-workers.Research has identified more than 40 carcinogenic substances emitted in tobacco smoke. Many ofthese substances are initiating agents (genotoxic) and are capable of inducing cancer by themselves atsufficient doses, others are recognized as promoters or cocarcinogens and act to enhance the activityof chemicals initiating the key genetic change. With so many different chemical carcinogens containedin cigarette smoke, it seems logical to ask if cigarette smoking is largely a phenomenon of initiationor promotion. If lung cancer due to cigarette smoking was the result of initiating carcinogens, theobserved risk should arguably be proportional to cumulative lifetime exposure, and the cessation ofcigarette smoking would not alter the already accumulated pack/year risk (i.e., one’s risk of cancer,once achieved, could not be decreased with abstinence). Current data, however, is contradictory to this