Effect of peroxisome proliiferators on intrachromosomal and interchromosomal recombination in yeast

Abstract

Peroxisome proliferators are a class of non-mutagenic hepatocarcinogens, which induce a similar pleiotropic response such as hepatomegaly, proliferation of the peroxisomes in hepatocytes and hepatocarcinogenesis. Peroxisome proliferators are not detectable by the Ames assay and various other short-term tests. Recently a system for intrachromosomal recombination in yeast (DEL) has been shown to be inducible by a variety of non-mutagenic carcinogens. These include many carcinogens that are not detectable by the Ames assay or by various other short-term tests. In the present study the peroxisome proliferators [4-chloro-6-(2,3-xylidino)-2-pyrimidinyl-thio]acetic acid (Wy-14,643); methyl-2-[4-(p-chlorophenyl)phenoxy]2-methyl propionate (methyl clofenopate); 2-methyl-2[p-(1,2,3,4-tetrahydro-1- naphthyl)phenoxy]-propionic acid (nafenopin); 2-[4-(2,2-dichlorocyclopropyl)phenoxy]2-methyl-propionic acid (ciprofibrate); [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio(N-beta-hydroxyethyl)-acetam ide] (BR-931); and ethyl alpha-p-chlorophenoxyisobutyrate (clofibrate) have been tested for their potential to induce DEL as well as interchromosomal recombination in yeast. No evidence for induction of either system has been found in the presence or the absence of the supernatant (S9) from rat liver homogenate. The data support the notion that peroxisome proliferators are truly non-mutagenic carcinogens.