Perhaps the most important question in cancer biology is what causes the cellular alterations
that produce a cancer. The answer to this question has been elusive. If the actual cause of these
alterations were known, the elimination of factors that produce cancer and the development
of better treatment modalities would likely follow. Cancer prevention might become a reality.
A cancerous growth has a number of predictable properties. The incidence rates of various
cancers are strongly related to environmental factors and lifestyle, and cancers have certain growth
characteristics, among which are the abilities to grow in an uncontrolled manner, invade surrounding
tissues, and metastasize. Also, when viewed microscopically, cancer cells appear to be
less well differentiated than their normal counterparts and to have certain distinguishing features,
such as large nuclei and nucleoli. Most cancers arise from a single clone of cells, whose
precursor may have been altered by insult with a carcinogen. In most cases cancer is a disease of
aging. The average age at diagnosis is over 65 and malignant cancers arise from a lifetime accumulation
of ‘‘hits’’ on a person’s DNA. These hits may result from genetic susceptibility to environmental
agents such as chemicals; radiation; or viral, bacterial, or parasitic infections; or from
endogenously generated agents such as oxygen radicals. It is often said that we would all get
cancer if we lived long enough. There is frequently a long latent period, in some cases 20 years or more, between the initiating insult and the appearance of a clinically detectable tumor. During this time, cellular
proliferation must occur, but it may originally be limited by host defenses or lack of access to the
host’s blood supply. During the process of tumorprogression, however, escape from the host’s
defense mechanisms and vascularization of the growing tumor ultimately occur.
The genetic instability of cancer cells leads to the emergence of a more aggressively growing
tumor frequently characterized by the appearance of poorly differentiated cells with certain
properties of a more embryonic phenotype. During tumor progression, considerable biochemical
heterogeneity becomes manifest in the growing tumor and its metastases, even though all the
neoplastic cells may have arisen originally from a single deranged cell. Any theory that seeks to
explain the initiation of cancer and its progression must take these observations into consideration.
In this chapter, we will examine what is known about various chemical, physical, and viral carcinogenic
agents and discuss the putative mechanisms by which they cause cancer.
