The advent of
new technologies in molecular biology and genomics now provide mechanistic toxicologists
with the tools to explore exactly how humans may differ from laboratory animals in their
response to toxic substances. These same tools are also being utilized to identify
individuals who are genetically susceptible to factors in the environment or respond
differently to a chemical exposure. For example, it is nowrecognized that a small percentage
of the population genetically lacks the ability to detoxify the chemotherapeutic drug, 6-
mercaptopurine, used in the treatment of some forms of leukemia. Young children with
leukemia who are homozygous for this genetic trait (about one in 300) may experience serious
toxic effects from a standard therapeutic dose of this drug. Numerous genetic tests for polymorphisms in drug metabolizing enzymes and transporters are now available that can
identify genetically susceptible individuals in advance of pharmacological treatment