PRINCIPLES OF TOXICOLOGY

314 CHEMICAL CARCINOGENESIS
Figure 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 times
higher for current female smokers compared to lifelong never-smokers. In addition to being
responsible 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 accounts
for at least 30 percent of all cancer deaths, is a major cause of heart disease, and is associated
with conditions ranging from colds and gastric ulcers to chronic bronchitis, emphysema, and
cerebrovascular disease.
The data surrounding smoking is particularly distressing for persons who might be occupationally
exposed to other substances as well. Asbestos-exposed workers who smoke reportedly contract lung
cancer at a rate that is 60 times that of persons not exposed to either substance. Other risk factors for
lung cancer may include exposure to arsenic, some organic chemicals, radon, radiation exposure from
occupational, medical, and environmental sources. Smokers who incur such exposures should be aware
of the increased risks they face compared to their nonsmoking co-workers.
Research has identified more than 40 carcinogenic substances emitted in tobacco smoke. Many of
these substances are initiating agents (genotoxic) and are capable of inducing cancer by themselves at
sufficient doses, others are recognized as promoters or cocarcinogens and act to enhance the activity
of chemicals initiating the key genetic change. With so many different chemical carcinogens contained
in cigarette smoke, it seems logical to ask if cigarette smoking is largely a phenomenon of initiation
or promotion. If lung cancer due to cigarette smoking was the result of initiating carcinogens, the
observed risk should arguably be proportional to cumulative lifetime exposure, and the cessation of
cigarette 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