Adaptation, drug resistance

Fig. 6 A plot showing 50% inhibitory drug concentration in vitro, in normal and drug-resistant lines, following treatments with vinblastine solution (n), or vinblastine encapsulated in liposomes ( ). The data suggest the possibility of the reversal of drug resistance by using carrier systems like liposomes. (Adapted in part from Ref...

Heterogeneity in the tumor cell population, promoted by genetic instability and ensuring the adaptive survival of a cell subpopulation which defines a drug-resistant trait... 

Generally, the formation of toxic metabolites is not the only pathway of biotransformation, and the overall metabolism is constituted toward detoxication and bioactivation processes. The toxic metabolites are themselves often further detoxified. The duality between a beneficial detoxication phenomenon (metabolism, drug resistance) and the occurrence of a toxic effect represents the cost for adaptability of metabolic enzymes to the diversity of xenobiot-ics. For those interested, a recent review applies the above chemistry to predict drug safety. 

Let us first consider adaptation to resist a toxic substance. Such a substance may well inhibit a particular set of enzymes. At first the synthesis of certain special parts of the cell will be retarded, and division may be impossible until some standard amount of the enzymes whose growth is retarded has in fact been built up. The drug thus delays multiplication. By the time division does occur, those parts of the cell which were not inhibited have attained more than their normal proportions, and yield a correspondingly enhanced concentration of their active intermediates. These in turn will finally be able to neutralize the action of the inhibitor itself. 

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