[Correlation of the ability of Di(2-ethylhexyl)phthalate to induce cell transformation, chromosome aberrations, and peroxisome proliferation in cultured Syrian hamster embryo cells].
Di(2-ethylhexyl)phthalate (DEHP), a commonly used plasticizer, induces peroxisome proliferation in liver cells and hepatocellular carcinomas in rodents. To study possible mechanisms for DEHP-associated cancer, we have measured induction of morphological transformation, chromosome aberrations, and peroxisome proliferation of cultured Syrian hamster embryo (SHE) cells. Molphological transformation was weakly induced by treatment with DEHP. The transformation frequency of DEHP was enhanced in the presence of rat liver postmitochondrial supernatant. DEHP induced chromosome aberrations in the cells only in the presence of exogenous metabolic activation. Clofibrate, a widely used hypolipidemic drug, failed to induce morphological transformation or chromosome aberrations. Treatment with [4-chloro-6-(2, 3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14, 643), which is a more potent carcinogen than DEHP or clofibrate, elicited a lower frequency of morphological transformation than DEHP in the presence of exogenous metabolic activation. Similar levels of peroxisome proliferation, as determined by an intensity of diaminobenzidine (DAB) staining, were observed in cultures treated for 2 hr with DEHP, clofibrate or Wy-14, 643. The results suggest a possible involvement of genetic damage by DEHP metabolites in induction of transformation of SHE cells. No clear relationship between inductions of peroxisome proliferation and cell transformation was observed.
Watanabe
E
E
Tsutsui
T
T
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects*; D006224:Cricetinae; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D008647:Mesocricetus; D008830:Microbodies / Q000187:drug effects
D004051:Diethylhexyl Phthalate