Rat hepatic vinyl chloride metabolites induce gene conversion in the yeast strain D7RAD in vitro and in vivo

Abstract

We have tested the genetic activity of gaseous vinyl chloride in vitro and in vivo using the gene-conversion system trp5-12/ trp5-27 → TRP +) in the yeast strain D7 RAD. To induce, in vitro, TRP + convertants with 2.5% gaseous vinyl chloride, a rat-liver microsomal system for metabolic activation of the vinyl chloride and dividing yeast cells are required. Neither a deficiency in excision repair ( rad3) nor in the error-prone repair pathway ( rad6) increased the vinyl-chloride-induced conversion frequencies compared with the repair-competent D7 RAD strain. When logarithmically growing cells of the D7 RAD strain were injected intravenously into male Wistar rats which inhaled 1% vinyl chloride in air for 24 h, a significant enhancement of the TRP + conversion frequencies was found compared with that in cells re-isolated from untreated rats. These results indicate that vinyl chloride metabolites from the metabolizing hepatocytes diffuse into yeast cells, which accumulate in the liver capillaries. This supports the hypothesis that the endothelial cells of the liver sinuses, which have hardly any metabolic activity, but give rise to vinyl-chloride-induced hemangiotheliomas (rate type of liver tumor), are transformed by diffusible metabolites of the procarcinogen vinyl chloride.