(Created 12/02)
UNL Environmental Health and Safety · (402) 472-4925 · http://ehs.unl.edu
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Epigenetic: These are carcinogens that do not act directly with genetic material. Several
types are possible:
• Cocarcinogen: Increases the overall response of a carcinogen when they are
administered together; for example, sulfur dioxide, ethanol, and catechol.
• Promoter: Increases response of a carcinogen when applied after the carcinogen
but will not induce cancer by itself; for example, phenol and dithranol.
• Solid-state:
Works by unknown mechanism, but physical form vital to effect; for
example, asbestos and metal foils.
• Hormone: Usually is not genotoxic, but alters endocrine balance; often acts as
promoter (e.g. DES and estrogens).
• Immunosuppressor: Mainly stimulates virally induced, transplanted, or metastatic
neoplasms by weakening host's immune system (e.g.,
antilymphocytic serum,
used in organ transplants).
Genotoxic carcinogens are sometimes effective after a single exposure, can act in a cumulative
manner, or act with other genotoxic carcinogens which affect the same organs. Some epigenetic
carcinogens, however, only cause cancers when concentrations are high and exposure long. The
implication is that while there may be a "safe" threshold level of exposure for some carcinogens,
others may have "zero" threshold; that is, one molecule of the chemical can induce a cancer.
Various
considerations indicate that DNA is a critical target for carcinogens:
• Many carcinogens are or can be metabolized so that they react with DNA. In these cases,
the reaction can usually be detected by testing for evidence of DNA repair.
• Many carcinogens are also mutagens.
• Inhibitors and inducers of carcinogens affect mutagenic activity.
• Chemicals often are tested for mutagenic and carcinogenic activity in the same cell
systems.
• Defects in DNA repair predispose to cancer development.
• Several inheritable or chromosomal abnormalities predispose to cancer development.
• Initiated dormant tumor cells persist, which is consistent with a change in DNA.
• Cancer is inheritable at the cellular level and, therefore, may result from an alteration of
DNA.
• Most, if not all, cancers display chromosomal abnormalities.
Although cancer ranks as the second most common cause
of death in the United States, the
process of carcinogenesis is not yet clearly defined. As a result, there are several problems
encountered when evaluating the carcinogenic potential of various agents in the environment.
First, human health can be affected by a wide range of factors including the environment,
occupation, genetic predisposition and lifestyle (i.e., cigarette smoking and diet). Therefore, it is
often difficult to determine the relationship between any one exposure and the onset of cancer.
Second, many cancers are latent responses; that is, the disease may not be manifested until many
years after the initial exposure. Third, the mechanisms for carcinogenesis
may differ according to
the type and the site of cancer.
