Most drugs have a limited dosage as a result of toxic side effects particularly following chronic use. Toxicity also occurs when higher doses are administered accidentally or deliberately.
Drugs chosen for their toxicity towards tumor cells can also cause toxicity towards normal tissues.
We are exploring ways of decreasing the toxicity of drugs and increasing their therapeutic specificity. These methods include the use of less toxic drug analogues, antidotes, improving the nutritional status of the patient and targeting of the drug to the tissue that requires therapy. The biochemical research techniques used include the monitoring of changes in biomolecules and cellular metabolism when drugs are administered in vivo, perfused intact organs, or incubated with intact cells or subcellular fractions. Cell systems studied include hepatocytes, tumor cell and neuron cultures. The synthesis of execution proteases may occur if death genes become activated or if apoptosis suppressor genes are down regulated.