Effect of peroxisome proliferator carcinogens on unscheduled DNA synthesis in rat hepatocytes determined by autoradiography

Cancer Lett. 1986 Dec;33(3):269-77. doi: 10.1016/0304-3835(86)90066-2.

Abstract

The potent peroxisome proliferator hepatocarcinogens WY-14,643, BR-931, and nafenopin, as well as mono(ethylhexyl)phthalate (MEHP), the principle metabolite of the weaker hepatocarcinogen di(2-ethylhexyl)phthalate) (DEHP), were evaluated in the in vitro rat hepatocyte DNA repair assay by quantitative autoradiography. None of these carcinogens induced unscheduled DNA synthesis (UDS). These results failed to confirm the previously reported induction of UDS by WY-14,643 and BR-931 as determined by nuclear liquid scintillation counting. Hydroxyurea (HU, 10 mM) is commonly employed to inhibit replicative DNA synthesis (RDS) when using scintillation counting techniques for UDS. Autoradiographs revealed incomplete inhibition of RDS by HU.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoradiography
  • Carcinogens*
  • Cell Division / drug effects
  • DNA Repair / drug effects*
  • Diethylhexyl Phthalate / analogs & derivatives
  • Diethylhexyl Phthalate / toxicity
  • In Vitro Techniques
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Microbodies / drug effects*
  • Nafenopin / toxicity
  • Pyrimidines / toxicity
  • Rats
  • Rats, Inbred F344

Substances

  • Carcinogens
  • Pyrimidines
  • Nafenopin
  • pirinixic acid
  • pirinixil
  • Diethylhexyl Phthalate
  • mono-(2-ethylhexyl)phthalate