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

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.