BIOLOGIC MARKERS IN URINARY TOXICOLOGY -- COPYRIGHT -- OTHER RECENT REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY -- PREFACE -- CONTENTS -- EXECUTIVE SUMMARY -- EFFECTS OF TOXIC EXPOSURE OF THE URINARY TRACT -- BIOLOGIC MARKERS OF SUSCEPTIBILITY AND EXPOSURE -- BIOLOGIC MARKERS OF EFFECT -- BIOLOGIC MARKERS IN EXTRAPOLATION -- NEW TECHNOLOGIES -- THE SUBCOMMITTEE'S RECOMMENDATIONS -- General -- The Kidney -- The Bladder -- The Prostate -- Biologic Markers of Exposure and Susceptibility -- Biologic Markers of Effect -- Use of Biologic Markers in Extrapolation -- New Technologies -- 1 INTRODUCTION -- BIOLOGIC MARKERS -- Markers of Exposure -- Markers of Effect -- Markers of Susceptibility -- VALIDITY OF BIOLOGIC MARKERS -- ETHICAL ISSUES -- STRUCTURE OF THE REPORT -- 2 TOXIC EXPOSURE OF THE URINARY TRACT -- THE URINARY TRACT -- Renal Blood Flow -- Glomerular Filtration -- Tubular Reabsorption and Secretion -- Hormonal Action -- MECHANISMS OF RENAL TOXICITY -- Susceptibility to Injury -- Direct Toxic Effects -- Renal Vascular Injury -- Glomerular Capillary Injury -- Renal Tubular-Cell Injury -- Indirect Toxic Effects -- Immunopathologic Mechanisms -- Xenobiotic Metabolism -- Necrosis and Apoptosis -- HOST FACTORS IN RENAL TOXICITY -- Changes with Renal Growth and Aging -- Changes with Diet -- Influence of Pre-existing Renal Function -- Nephron Number at Birth -- Acute Renal Disease -- Chronic Renal Disease -- Physiologic Responses to Renal Injury -- Physiologic Changes with Compensatory Hypertrophy -- Factors Associated with Progressive Low of Renal Function -- CLINICAL EFFECTS OF CHEMICAL EXPOSURE ON THE KIDNEY -- Acute Renal Failure -- Tubulointestitial Nephritis -- Chronic Glomerulonephritis -- Rapidly Progressive Glomerulonephritis -- Nephrotic Syndrome -- Hypertension -- CANCER OF THE BLADDER, KIDNEY, AND PROSTATE.

Tumor-Suppressor Genes, Oncogenes, and Growth Factors -- Cancer of the Bladder -- Cancer of the Kidney -- Cancer of the Prostate -- Interstitial Cystitis -- ANIMAL MODELS OF INTERSTITIAL CYSTITIS -- SUMMARY -- 3 BIOLOGIC MARKETS OF SUSCEPTIBILITY AND EXPOSURE -- POPULATIONS AT RISK -- Hereditary Susceptibility to Nephrotoxicity -- Nutrition -- Socioeconomic Factors -- Age -- Coexisting Chronic Disease -- Addictive Behavior and Recreational Drug Use -- Occupational or Environmental Exposure -- MARKERS OF SUSCEPTIBILITY -- Modifying Factors of Susceptibility -- Parenchymal Renal Disease -- Cytochrome P-450-Dependent Activation of Nephrotoxicants -- Prostaglandin H Synthase-Dependent Activation of Nephrotoxicants -- Glutathione-Dependent Activation of Nephrotoxicants -- Extrarenal Conjugation and Interorgan Metabolism -- GSH Conjugation of Halogenated Alkanes and Alkenes by Cytosolic and Microsomal GSH S-Transferases -- Cysteine Conjugate Beta-Lynse-Dependent Bioactivation -- In Vivo Toxicity of S-Conjugates -- Role of Cysteine Conjugate Beta-Lyase in Bioactivation of Cysteine S-Conjugates -- Other Enzymes Involved in Cysteine S-Conjugate Metabolism -- Susceptibility Factors in Cancers of the Genitourinary Tract -- Cancer of the Kidney -- Familial and Sporadic Nonpapillary Renal-Cell carcinoma -- Papillary Renal-Cell Carcinoma -- Cancer of the Bladder -- Karyotypic Studies -- Metabolic Pathways and Susceptibility to Bladder Cancer -- DNA Adducts -- Acquired Conditions Predisposing to Bladder Cancer -- Cancer of the Prostate -- Population Studies -- Karyotypic Analysis -- MAKERS OF EXPOSURE -- SUMMARY -- 4 BIOLOGIC MAKERS OF EFFECT -- EXTERNAL VISUALIZATION -- URINARY CLEARANCE MEASUREMENTS -- Direct -- Indirect -- URINALYSIS -- Total Urinary Solute Concentration -- Dipsticks -- Microscopic Analysis -- Proteinuria -- Measurement of Urinary Protein.

Albuminuria -- Microalbuminuria -- Low-Molecular-Weight Proteinuria -- Brush-Border Proteins -- Tamm-Horsfall Protein -- MARKERS OF CYTOTOXICITY AND CELLULAR RESPONSE -- Urinary Cells -- Markers of Injury or Inflammation in Renal-Tissue Samples -- Markers of Renal-Tissue Injury in Urine -- Urinary Enzymes -- Theoretical and Diagnostic Importance -- Disadvantages as Markers -- MARKERS OF NEOPLASIA -- General Considerations -- Proliferation -- Renal-Cell Carcinoma -- Bladder Cancer -- Conventional Markers in Bladder Cancer -- Dipstick Testing -- Cytologic Analysis -- Karyotypic changes -- Markers in Occupationally Exposed Cohorts -- Prostatic Cancer -- Serum Prostate-Specific Antigen -- Prostatic Intraepithelial Neoplasia -- DNA Ploidy and Prostatic Cancer -- Cytoskeletal and Nuclear-Matrix Proteins -- Tumor-Suppressor Genes -- Growth Factors -- MARKERS OF INTERSTITIAL CYSTITIS -- SUMMARY -- 5 BIOLOGIC MARKERS IN EXTRAPOLATION -- BASIS OF EXTRAPOLATION -- Animal Studies -- Renal Parenchymal Injury -- Glomerular Filtration Rate -- Tubular Function -- Proteinuria -- Tamm-Horsfall Protein -- Enzymuria -- Monoclonal Antibodies -- Bladder Toxicity -- Xenobiotics -- Extracellular Calcium -- Zinc -- Monovalent-Cation Salts and Urinary pH -- Mechanical Distention -- Growth Factors -- Treatment -- Renal-Tumor Formation -- TECHNIQUES USED IN RISK ASSESSMENT -- Animal Studies -- Whole-Kidney Preparations -- In Vitro Studies -- Uses and Limitations of Freshly Isolated Renal Cells -- Renal-Cell Cultures as Models of Chronic Injury and Carcinogenesis -- In Vitro Models of Nonrenal Urinary Epithelia -- IMPROVED RISK-ASSESSMENT EXTRAPOLATION -- Relevance of Test Systems -- Metabolism and Kinetics -- Mechanism of Action -- Quantitative Issues -- SUMMARY -- 6 NEW TECHNOLOGIES -- MAKERS OF CELL INJURY, REGENERATION, AND HYPERTROPHY -- The Cell Cycle -- Growth Factors.

Epidermal Growth Factor -- Insulin-Like Growth Factors -- Transforming Growth Factor Beta -- Angiotensin II -- Early-Response Genes -- Nucleic Acid Synthesis and Hypertrophy -- Sodium-Pump Activity and Cell Growth -- Polyamines -- CANCER OF THE BLADDER -- Cell Culture -- Quantitative Fluorescence Image Analysis -- DIFFERENTIAL-DISPLAY POLYMERASE CHAIN REACTION -- CANCER OF THE PROSTATE -- Prostate-Specific Antigen -- Marker Development -- Neuroendocrine Cells in the Prostate -- CANCER OF THE KIDNEY -- Renal Tumors in Male Rats Mediated by Alpha2u-globulin -- Acute Nephropathy -- Chronic Renal-Cell Injury and Proliferation -- Renal Neoplasia -- Genotoxicity -- Related Proteins and Their Role in Safety Evaluation -- Male Rat Renal Tumors in the Assessment of Risk to Humans -- SUMMARY -- 7 CONCLUSIONS AND RECOMMENDATIONS -- TOXIC EXPOSURE OF THE URINARY TRACT -- The Kidney -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- The Bladder -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- The Prostate -- Conclusion -- Recommendation -- BIOLOGIC MARKERS OF EXPOSURE AND SUSCEPTIBILITY -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- BIOLOGIC MARKERS OF EFFECT -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- USE OF BIOLOGIC MARKERS IN EXTRAPOLATION -- Conclusion -- Recommendation -- NEW TECHNOLOGIES -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- Conclusion -- Recommendation -- REFERENCES.