Evaluation of toxic and genotoxic effects of xenobiotica by means of a liver perfusion system

• An isolated liver perfusion system is described in which mammalian cells, as genetic targets, can be directly and continuously exposed to the perfusate at varying distances from the metabolising organ. Thus, potentially mutagenic metabolites released from the liver can be detected, and the biological half-life of the reactive metabolites can be estimated. Bile samples can be collected repeatedly and tested for mutagenic activity. It is also possible to study the biotransformation and excretion of a chemical and/or its metabolites by collecting simultaneously perfusate and bile samples for analysis. Furthermore, possible effects on different liver functions can be investigated.In this liver perfusion/cell culture system, some chemically different compounds have been studied. Of these chemicals, benzo(a)pyrene and styrene-7,8-oxide did not exert any detectable mutagenic effects. Dimethylnitrosamine, on the other hand, was highly mutagenic to V79 cells exposed in the effluent perfusate close to the liver, whereas styrene gave rise to a weaker mutagenic effect which, however, was detected in V79 cells exposed at any site in the perfusion system. 1,1-DimethyIhydrazine caused a mutagenic effect in the perfusate and bile from selenium-deficient livers. With selenium supplemented livers a mutagenic effect was only obtained in the perfusate.Benzo(a)pyrene caused no effects on the liver functions investigated. Dimethylnitrosamine reduced protein synthesis and N,N-dimethylaniline metabolism. Styrene reduced the bile flow, whereas styrene-7,8-oxide increased it. However, bile acid excretion was not affected by either test compound. 1,1-DimethyIhydrazine increased the lactate/pyruvate level in the perfusate.

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NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

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