DOSE-RESPONSE CURVES FOR AGENTS THAT IMPAIR CELL REPRODUCTIVE INTEGRITY - A FUNDAMENTAL DIFFERENCE BETWEEN DOSE-RESPONSE CURVES OR ANTIMETABOLITES AND THOSE FOR RADIATION AND ALKYLATING AGENTS

Many commonly used antitumour and immunosuppressive agents act by impairing the reproductive integrity of proliferating cells. The common assumption that the relation between dose and cell survival for such agents is generally exponential is incorrect. The dose-response curve for antimetabolites is shown to be characteristically hyperbolic, i.e. the product of the surviving fraction of a proliferating cell population and the dose of agent (or a power of the dose) is a constant. The hyperbolic form of these curves is probably due to the competitive nature of antimetabolite action. Alkylating agents resemble radiation in showing exponential dose-response curves. Such curves may be expected when discrete quanta of agent react independently and at random with critical cell targets. © 1969, The British Empire Cancer Campaign for Research. All rights reserved.