PRINCIPLES OF TOXICOLOGY

13 Chemical Carcinogenesis
CHEMICAL CARCINOGENESIS
ROBERT C. JAMES and CHRISTOPHER J. SARANKO
There are few people living today who have not been affected in some way by cancer, through either
personal experience or that of a family member. Current statistics indicate that one out of two men and
one out of three women in the United States will develop cancer over the course of their lifetime.
Approximately 1.2 million people will be diagnosed with cancer this year alone, and this number
excludes common and easily treatable basal and squamous cell skin cancers. While long-term survival
rates are improving, cancer is still the second leading cause of death in the United States behind heart
disease. In 1999, one of every four deaths or approximately 560,000 will be from cancer. In addition
to the price cancer exacts in human lives lost, economic costs are estimated to be a staggering 107
billion dollars per year. This figure includes direct medical expense as well as the cost of lost
productivity due to increased morbidity and early death. Clearly, there are many reasons for modern
society to be concerned about cancer.
The disease we call cancer is actually a family of diseases having the common characteristic of
uncontrolled cell growth. In normal tissue, there are a myriad of regulatory signals that instruct cells
when to replicate, when to enter a resting state, and even when to die. In a cancer cell these regulatory
mechanisms become disabled and the cell is allowed to grow and replicate unchecked. Cancer is largely
a disease of aging. The overwhelming majority of cancers are first diagnosed when patients are well
over the age of 50. Carcinogenesis, or the sequence of events leading to cancer, is a multistep process
involving both intrinsic and extrinsic factors. We know this because certain individuals inherit a genetic
predisposition to certain types of cancer. The majority of cancers, however, are not associated with
any particular inheritance pattern. Still, many of the same steps have been implicated. These incremental
steps typically occur over the span of decades.
At the most fundamental level, cancer is caused by abnormal gene expression. This abnormal gene
expression occurs through a number of mechanisms, including direct damage to the DNA and
inappropriate transcription and translation of cellular genes. Carcinogenesis has been shown to be
induced or at least accelerated by exposure to certain types of chemicals. These chemicals are known
as carcinogens. In the pages that follow, we will discuss the carcinogenic process and how chemicals
can contribute to that process.
This chapter will discuss:
• Tumor classification and nomenclature
• Properties of carcinogenic chemicals
• An overview of the molecular basis of carcinogenesis
• Methods for testing chemicals for carcinogenic activity
• Chemicals identified as human carcinogens
• Risks associated with occupational carcinogens
• Factors that modulate carcinogenic risk
Principles of Toxicology: Environmental and Industrial Applications, Second Edition, Edited by Phillip L. Williams,
Robert C. James, and Stephen M. Roberts.
ISBN 0-471-29321-0 © 2000 John Wiley & Sons, Inc.
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