Influence of vinyl chloride monomer (VCM) and As2O3 on rat liver cell proliferation after partial hepatectomy

Abstract

Male Wistar rats (240–320 g b. wt.) were partially (2/3) hepatectomised and immediately thereafter exposed to inhalation over 28 h of vinyl chloride monomer (VCM) at concentrations of 0, 50, 125, and 500 ppm. An investigation was also performed in which, following partial hepatectomy, rats of 130–150 g b. wt. were infused by the caudal vein over 28 h with As₂O₃ (AT) at concentrations of 0, 1, 2, and 10 mg/ml. The total volume of the infusion was 16.8 ml.

Following treatment, the liver was removed and investigations were made of proliferative activity in the tissue. With preparations from VCM-treated animals, investigations were made of the mitotic index (histologically), the ³H-thymidine index (autoradiographically), and the incorporation of ³H-thymidine in DNA (using liquid-scintillation counting). Further investigations were made of DNA synthesis in nuclei of these tissues by impulse-cytophotometry determining the proportions of cells in S-phase to those in G₁. Incorporation of ³H-thymidine and mitotic activity was also determined using tissue from AT-treated animals. The tissue alkaline phosphatase activities in liver preparations both from VCM- and AT-treated animals were also measured.

In all measured parameters, an increase was observed over values found in controls and those increases were dose-related. The results indicate that administration of VCM or AT leads to stimulation of cell proliferation in regenerating rat liver. However, increase of alkaline phosphatase activity could not be referred to preferential effects of VCM and AT on endothelial cells. As shown by histochemical investigations, the alkaline phosphatase activity was localised mainly in bile-duct canaliculi — not in sinusoids.