Cohen S M
University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha 68198-3135, USA.
Food Chem Toxicol. 1995 Sep;33(9):715-30. doi: 10.1016/0278-6915(95)00040-9.
Urine is a complex mixture of numerous substances, only some of which are described above. Literally thousands of substances have been identified in normal urine, including a variety of ions, non-ionic substances and macromolecules. Their presence and concentrations are highly variable, dependent on fluid intake and on nutritional, physiological and biochemical influences. Marked diurnal variations exist. Methodologies involved in the collection and analysis of these components can greatly influence the interpretation of the results. The influence of these various parameters in the urine on bladder carcinogenicity can be either direct or indirect. A major difficulty in studying this aspect of urothelial carcinogenesis is that it is essentially impossible to alter only one variable in the urine at a time. Alteration of any one variable results in physiological alteration of several other of the constituents in the urine. In addition, the processes involved in urothelial carcinogenesis frequently involve a complex interaction of multiple variables, such as volume, osmolality, cationic concentration, anionic concentration, quantitative and qualitative differences in protein, and generation of precipitate, crystals or calculi. Thus, it is likely that the actual mechanisms involved in the carcinogenic process with many of these chemicals, particularly those that are non-genotoxic, will involve a complex interaction of several constituents of the urine. Although this poses a formidable obstacle to our understanding in experimental situations as well as in extrapolating to humans, the role of specific factors appears to be discernible and should offer insight into the risk assessment process (Cohen and Ellwein, 1991 a,b and 1992).
尿液是多种物质的复杂混合物，上述仅描述了其中一些。正常尿液中已鉴定出 literally 数千种物质，包括各种离子、非离子物质和大分子。它们的存在和浓度变化很大，取决于液体摄入量以及营养、生理和生化影响。存在明显的昼夜变化。这些成分的收集和分析所涉及的方法会极大地影响结果的解读。尿液中这些各种参数对膀胱致癌性的影响可以是直接的，也可以是间接的。研究尿路上皮癌发生这一方面的一个主要困难在于，基本上不可能一次只改变尿液中的一个变量。任何一个变量的改变都会导致尿液中其他几种成分的生理改变。此外，尿路上皮癌发生过程中涉及的过程通常涉及多个变量的复杂相互作用，如体积、渗透压、阳离子浓度、阴离子浓度、蛋白质的定量和定性差异以及沉淀物、晶体或结石的形成。因此，许多这些化学物质，特别是那些非遗传毒性物质，致癌过程中实际涉及的机制可能涉及尿液中几种成分的复杂相互作用。尽管这在实验情况下以及外推至人类时给我们的理解带来了巨大障碍，但特定因素的作用似乎是可辨别的，并且应该为风险评估过程提供见解（科恩和埃尔温，1991a、b 和 1992）。
