Mediation of organ specificity in chemical carcinogenesis

Organ and species specificity in the experimental induction of cancer by chemical agents has been widely observed and is incompletely understood even though the phenomenon has become a persistent puzzle in oncology. Animal model experiments and epidemiological data on human cancer morbidity from environmental causative agents would lead to the conclusion that some organs are more susceptible because they tend to concentrate and (or) retain a given agent more than other tissues. The routes of administration or unique features in the metabolism of the agent explain the differences in some instances only. We propose an additional general mechanism: an organ (or cell type) may be specifically and differentially susceptible to the action of an agent if, by happenstance, a major storage or secretory protein constituent of the cell binds the agent in question reversibly, thereby concentrating or retaining the agent.