Date of Award

Spring 1972

Document Type

Thesis

Department

Life & Environmental Sciences

First Advisor

James Manion

Second Advisor

Guido Bugni

Third Advisor

Vincent Palese Jr.

Abstract

An increasing number of reports during the Dast decade have suggested a positive, though far from perfect, correlation between carcinogenicity and the ability of a side variety of carcinogens to impair the immune status of the host. In addition, those conditions resulting in the suppression of the immune reaction of the host, including the use of immunosuppressive drugs with transplant patients, seem to foster the incidence of cancer [St jernsward, 1969]. Burnet [1961] has suggested that the evolutionary significance of the immune response is that it enables the elimination of mutant somatic cells, which might otherwise form neoplasms. Then, possibly carcinogens have a dual mechanism, on one hand causing the production of abnormal cells, and on the other, interfering with the surveillance mechanisms of the host that may otherwise have eliminated those cells. Surely the most potent ’’theoretical'’ carcinogen would be one capable of both, but as Klein [i960] has noted, both need not necessarily be a part of a single action. Immunosuppression could, then, be a "secondary" mechanism permitting the survival and growth of the possibly antigenic tumor cells produced by the "primary" action of the carcinogen.

A number of complex hydrocarbons have been shown to be capable of both initiating tumors and depressing antibody levels in experimental animals. An although the mechanisms through which they accomplish such feats are far from simple and little understood, chemical carcinogens lend themselves to study much more easily than physical or viral carcinogens; they are far more predictable, and their mechanisms, through studies of their chemical properties, may more easily be decoded.

A number of questions arise from these relationships: What is the correlation between carcinogenicity and suppressive ability and what do these two processes share that causes the correlation. What property is it that chemical, physical, and viral carcinogens hold in common that allows them to perform essentially the same actions? Do carcinogens differ from other antigens in respect to their effect on the immune system, and if so, why? When in the course of cancer does immunologic suppression first become manifest, and which facets of the immune system does it effect? My study has been performed with and in reference to chemical carcinogens and has been directed toward the last of the questions posed above. Specifically, then, my inquiry deals with 3-methylcholanthrene*, its carcinogenic abilities and its effect on the immune response.

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