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Metabolic Regulatory Circuits and Carcinogenesis

( McArdle Memorial Laboratory, The Medical School, University of Wisconsin, Madison, Wisconsin)

Recent studies on the control of enzyme synthesis and activity in microorganisms which have been carried out largely in the laboratory of Jacob and Monod in Paris have led to the formulation of a model which in its general form agrees with much of the known experimental data. Basically, the genetic apparatus for enzyme synthesis is thought to consist of regulator genes which produce cytoplasmic products known as repressors and an operon consisting of an operator and structural genes. The product of the regulator gene together with small molecular weight, usually exogenous, regulators interacts with the operator gene to control the expression of the entire operon. This basic circuit may be modified in a number of ways to produce an equally varied number of phenotypes. Several of these phenotypes may be perpetuated by a short exposure of the regulator, here thought of as a carcinogen, to the system. Such a picture fits the known concepts of chemical carcinogenesis and shows in a theoretical manner how a malignant cell may be produced in the absence of a genetic (DNA) change. If malignancy is not the result of a direct gene (DNA) mutation, a reversion from the malignant to the nonmalignant state is well within reason.

^* American Cancer Society Professor of Oncology.

Received 6/25/63.

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