Trichioroethylene and Chioral Hydrate Metabolism in the Japanese Medaka Minnow (Oryzias Latipes) In Vitro

摘要

The drive to assess more potential human health and environmental problems, coupled with decreasing budgetary resources has led to the investigation of alternative test methods. For an alternative method to be developed, relevancy to the target organism (in this case, the human) should be critically evaluated. The Japanese medaka (Oryzias latipes) is a small fish species which has some very district advantages: the species is small enough to be reared in large numbers under relatively simple environmental conditions, the gestation period is short so that many generations can be tested in a short period, its size enables the histological examination of multiple organ systems from a single prepared slide, its growth and development have been well characterized, and it appears to respond in a predictable manner to environmental carcinogens. However, in the assessment of compounds which are metabolized to be come toxic, the relevance of the medaka as a surrogate for the human has been less well-characterized. While some previous investigations have examined the soluble enzyme system, none to date have evaluated the cytochrome P-450 system, a system restricted to the endoplasmic reticulum of the cell. Because of the environmental prominence of trichloroethylene (TRI) and the role of metabolism in the toxicity of TRI, we sought to determine the capacity of the Japanese Medaka to metabolize this compound. In experiments conducted in vitro, we have determined that TRI is metabolized to the same metabolite (chloral hydrate, CH) as initially formed by the microsomal P-450 systems expressed in mammalian cells. Further, in medaka preparations, CH is metabolized to the same metabolites as are produced by mammalian enzyme systems.