Toxicity, tumor promotion, and carcinogenesis in relation to excessive dosage.

Excessive dosage of many toxic compounds leads to a response by those exposed cells in the form of toxic hyperplasia. This toxicity often is a result of oxidation and peroxidation products that affect multiple sites of critical importance in the cell from the membrane of DNA itself. Some of these products are both mutagenic and carcinogenic and can affect key enzymes of defense and proliferation. Chronic toxicity of this type can deplete or inactivate endogenous defense systems that would normally prevent the formation of these toxic products. Subtoxic doses will not significantly compromise cellular defense systems and are far less likely to induce the critical events associated with hyperplasia, tumor promotion, and the expression of a "carcinogenic" effect. The many new discoveries in oxidation and peroxidation toxicity open up a greater awareness of the potential problems of interpretation associated with excessive dosage in evaluation of compounds for carcinogenicity.