Iatrogenic disease, drug metabolism, and cell injury: lethal synthesis in man.

One important consideration to be appreciated from the examples of "lethal synthesis" presented in this paper is that the mechanisms of toxic substances must be further explored, a true understanding of the complex modalities of cellular injury achieved, and the significance of cellular changes determined before we can preestablish the hazards of chemical or environmental contaminants. The identification of compounds that may modify the intracellular milieu by adduction of marcromolecules and those that may be activated to produce proximate toxins could be accomplished on the basis of their distinguishing structure and metabolism. Assaying for the levels and functions of xenobiotic systems may help us to preduct the potential risk to individuals. It is incumbent upon us now to become more critical of the side-effects of "therapy", to weigh the jeopardy against the benefits involved. And to do so, we must attain a better comprehension of the complicated mechanisms of cellular injury.