Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Synergistic exposures

AL Frank MD

University of Texas Health Center at Tyler, Tyler, TX,

Increasingly, carcinogenesis theory clarifies the multifactorial nature of cancer, and the biological complexity that proceeds from normal to malignant tissue. Further adding to this complexity is the realization of the synergistic effects of two or more cancer-causing agents producing many more cases of cancer than would result from the additive effects of these agents. Selikoff and colleagues first documented the synergistic effects of asbestos and cigarette smoke exposures for the development of lung cancer, although not for mesothelioma. Others soon added to this observation and documented that the same occurred with cigarette smoke and radiation exposures producing more lung cancer, while others noted the synergistic relationship of smoking with alcohol use in producing oro-pharyngeal cancers. More recent studies continue to document these epidemiologic findings, but cell studies are now documenting these changes as well. For example, there is an increase in abnormal cells found among nurses exposed to cytotoxic agents as well as cigarette smoke. Suggestions have been made that mixtures of pesticides are more carcinogenic than exposures to single compounds, and other personal habits such as betel quid chewing may also be involved synergistically in the production of human cancers, taking the problem outside the workplace setting. Traditional research methods look at individual compounds and their singular effects; it is now increasingly clear that mixtures of materials need to be assessed at the same time to more fully appreciate possible synergistic interactions. This may ultimately lead to a fuller understanding of the mechanistic aspects of carcinogenesis, for a wide range of cancer-causing agents.

KEY WORDS: multiplicative, synergistic, asbestos, cigarette smoke, radiation.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on environment & lifestyle.