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INTRODUCTION

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The majority of cancers are multifactorial in etiology, the result of a combination of genetic and nongenetic factors. Genetic factors alone are estimated to cause only about 5% of cancers. Nongenetic factors, sometimes referred to as environmental factors, account for the majority of cancers. They include lifestyle factors such as tobacco use, alcohol consumption, poor diet, obesity, physical inactivity, and occupational and consumer exposures to myriad chemicals and product formulations, which collectively contribute to the occurrence of a substantial proportion of cancers. Millions of US workers are exposed to substances that are known to cause cancer in humans, with 125 documented chemical/exposure circumstances, and more that cause cancer in animal studies. Unfortunately, however, less than 5% of chemicals manufactured or processed in the United Sates have been tested for carcinogenicity in animal bioassays. Based on associations between occupational exposures and cancer, it is estimated that 4–10% of US cancers are caused by occupational exposures.

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The identification of occupational carcinogens is important in part because most occupational cancers are completely preventable with appropriate exposure controls, personnel practices, and strict protective legislation. Various agencies have classified chemicals and other agents as to their potential carcinogenicity to humans and animals, including the International Agency for Research on Cancer (IARC), an independent scientific institution within the World Health Organization (WHO) (see http://www.iarc.fr/). Further classifications of carcinogenic agents may be found on the Web site of the U.S. National Toxicology Program (http://ntp.niehs.nih.gov/) and in its most recent report on carcinogens (12th Report on Carcinogens).

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CARCINOGENESIS: FUNDAMENTAL PROPERTIES

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Evidence suggests that cancers arise from a single abnormal cell. The initial stage in development of the abnormal cell appears to result from an alteration or mutation in the genetic material, deoxyribonucleic acid (DNA). This alteration may occur spontaneously or may be caused by exogenous factors, such as exposure to carcinogenic chemicals or radiation. Whether a tumor develops from this altered cell may depend on a variety of factors, such as the ability of the cell to repair the damage, the presence of other endogenous or exogenous agents that foster or inhibit tumor development, and the integrity of the immune system.

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Stages in Tumor Development

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A variety of evidence indicates that cells undergo multiple heritable changes in the process of becoming a “cancer cell”; this process is termed carcinogenesis. Early animal studies investigating the etiology of cancer cell growth hypothesized that tumor development involved at least two distinct stages: initiation and promotion. A classic example of this process is the mouse skin tumor model. In this model, a small dose of a carcinogen, known as the initiator (in this case, typically a polycyclic aromatic hydrocarbon [PAH]) is applied to the skin. Although large doses of PAHs alone readily induced skin tumors, the smaller doses alone did not. However, application of a promoter, such as croton oil, following ...

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