Induction of sister-chromatid exchanges by direct and indirect mutagens in human lymphocytes, co-cultured with intact rat liver cells. Effect of enzyme induction and preservation of the liver cells by freezing in liquid nitrogen

Abstract

An in vitro assay system using intact rat hepatocytes and human peripheral lymphocytes is described which has been developed with the aim of bringing test conditions closer to in vivo conditions, thereby broadening the available battery of simple in vitro assays. A culture vessel, which contains an inner chamber with a semipermeable bottom, has been designed to allow easy removal of the hepatocytes. Determination of sister-chromatid exchange rate was used as the experimental end point. For validation, a series of chemicals were used which have been tested previously in a large interlaboratory investigation of short-term test methods. Our study supplies complementary information to this investigation in as much as some chemicals could be correctly assigned as positive or negative, in contrast to what was found in the earlier tests. Furthermore, we show that the metabolic capacity of both normal and induced liver cells can be preserved in liquid nitrogen for long periods.