studies have demonstrated the presence of similar lead-binding proteins in human kidney, liver, and brain cytosolic fractions (Kahng et al., 1992). Further research is needed to determine the possible roles of these proteins in mediating the observed increase (Steenland et al., 1992) in renal cancer in persons occupationally exposed to lead.

SUMMARY

New technologies using modern advances in molecular biology, genetic engineering, in vitro tissue-culture systems, and animal-model systems provide a wide variety of new methods that can be applied to biologic-marker research. The new technologies are rapidly being integrated into strategies for biologicmarker research pertaining to the genitourinary tract and, in a broader perspective, to other organ systems as well. The potential number of biologic markers is enormous. Each newly identified marker will require careful evaluation before its use in human population studies.

Several important lessons have been learned from the use of PSA as a clinical biologic marker for prostatic cancer. The uncertainties associated with its use have emphasized the need for the cooperation of various disciplines—including biostatistics and epidemiology, the basic sciences, and clinical specialties—to review the utility of specific biologic markers before their integration into clinical practice.

Extensive studies have attempted to extrapolate data concerning alpha2u-globulin from animal studies to human conditions, such as nephrotoxicity and renal cancer. The results emphasize the need for caution in the extrapolation of in vitro and nonhuman in vivo studies to humans. At the same time, it is notable that potential biologic markers, such as alpha2u-globulin, can be studied in relation to environmental stress. Some markers are quantifiable at the singlecell level, and the interactions of various cells can be investigated. New technologies—such as differential PCR, quantitative in situ PCR, and quantitative fluorescence image analysis (QFIA)—facilitate the use of biologic markers to describe genotypic and phenotypic changes associated with xenobiotic exposure.

New technologies can also promote the study of biologic markers at the cellular level. Particularly important are the changes that occur in nucleic acid synthesis, which regulate cell growth and death and which enhance our understanding of carcinogenesis, nephrotoxicity, and other diseases of the genitourinary tract.



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