142
U N I T 1
Cell and Tissue Function
one of the most important host responses for controlling
the growth of tumor cells. The finding of tumor-reactive
antibodies in the serum of people with cancer supports
the role of the B lymphocyte as a member of the immune
surveillance team. Antibodies cause destruction of can-
cer cells through complement-mediated mechanisms
or through antibody-dependent cellular cytotoxicity,
in which the antibody binds the cancer cell to another
effector cell, such as the NK cell, that does the actual
killing of the cancer cell. NK cells do not require antigen
recognition and can lyse a wide variety of target cells.
Chemical Carcinogens
A carcinogen is an agent capable of causing cancer. The
role of environmental agents in causation of cancer was
first noted in 1775 by Sir Percivall Pott, a English physi-
cian who related the high incidence of scrotal cancer in
chimneysweeps to their exposure to coal soot.
2,3
Coal
tar has since been found to contain potent polycyclic
aromatic hydrocarbons. Since then, many chemicals
have been suspected of being carcinogens. Some have
been found to cause cancers in animals, and others are
known to cause cancers in humans (Chart 7-1).
Chemical carcinogens can be divided into two
groups: (1) direct-reacting agents, which do not require
activation in the body to become carcinogenic, and
(2) indirect-reacting agents, called
procarcinogens
or
initiators,
which become active only after metabolic
conversion.
2,3
Direct- and indirect-acting initiators form
highly reactive species (such as free radicals) that bind
with residues on DNA, RNA, or cellular proteins. They
then prompt cell mutation or disrupt protein synthesis
in a way that alters cell replication and interferes with
cell regulatory controls. The carcinogenicity of some
chemicals is augmented by agents called
promoters
that,
by themselves, have little or no cancer-causing ability. It
is believed that promoters, in the presence of these car-
cinogens, exert their effect by altering gene expression,
increasing DNA synthesis, enhancing gene amplification
(i.e., number of gene copies that are made), and altering
intercellular communication.
Exposure to many carcinogens, such as those con-
tained in cigarette smoke, is associated with a lifestyle
risk for development of cancer. Cigarette smoke con-
tains both procarcinogens and promoters. It is directly
associated with lung and laryngeal cancer and has been
linked with cancers of the mouth, nasal cavities, phar-
ynx, esophagus, pancreas, liver, kidney, uterus, cervix,
and bladder and myeloid leukemias. Not only is the
smoker at risk, but others passively exposed to cigarette
smoke are at risk. Chewing tobacco increases the risk of
cancers of the oral cavity and esophagus.
Occupational exposure to industrial chemicals is
another significant risk factor for cancer. These include
polycyclic aromatic hydrocarbons, which are metabo-
lized in the liver.
5
For example, long-term exposure to
vinyl chloride, the simple two-carbon molecule that is
widely used in the plastics industry, increases the risk for
hepatic angiosarcoma.
3
There is also strong evidence that certain elements in
the diet contain chemicals that contribute to cancer risk.
Most known dietary carcinogens occur either naturally
in plants (e.g., aflatoxins) or are produced during food
preparation.
2
The polycyclic aromatic hydrocarbons are
of particular interest because they are produced during
several types of food preparation, including frying foods
in animal fat that has been reused multiple times; grill-
ing or charcoal-broiling meats; and smoking meats and
fish. Nitrosamines, which are powerful carcinogens, are
formed in foods that are smoked, salted, cured, or pick-
led using nitrites or nitrates as preservatives. Formation
of these nitrosamines may be inhibited by the presence
of antioxidants such as vitamin C found in fruits and
vegetables. Cancer of the colon has been associated with
high dietary intake of fat and red meat and a low intake
of dietary fiber.
28
A high-fat diet is thought to be car-
cinogenic because it increases the flow of primary bile
acids that are converted to secondary bile acids in the
presence of anaerobic bacteria in the colon, producing
carcinogens or promoters.
Heavy or regular alcohol consumption is associ-
ated with a variety of cancers. The first and most toxic
metabolite of ethanol is acetaldehyde, a known car-
cinogen that interferes with DNA synthesis and repair
and that causes point mutations in some cells.
28,29
The
carcinogenic effect of cigarette smoke can be enhanced
CHART 7-1
Major Chemical Carcinogens
2,3
Direct-Acting Alkylating Agents
■■
Anticancer drugs (e.g., cyclophosphamide, cisplatin,
busulfan)
Polycyclic and Heterocyclic Aromatic
Hydrocarbons
■■
Tobacco combustion (cigarette smoke)
■■
Animal fat in broiled and smoked meats
■■
Benzo(a)pyrene
■■
Vinyl chloride
Aromatic Amines and Azo Dyes
■■
β
-Naphthylamine
■■
Aniline dyes
Naturally Occurring Carcinogens
■■
Aflatoxin B1
■■
Griseofulvin
■■
Betel nuts
Nitrosamines and Amides
■■
Formed in gastrointestinal tract from nitro-stable
amines and nitrates used in preserving processed
meats and other foods
Miscellaneous Agents
■■
Asbestos
■■
Chromium, nickel, and other metals when volatilized
and inhaled in industrial settings
■■
Insecticides, fungicides
■■
Polychlorinated biphenyls
