The initiating and promoting effects of trichloroethylene in rat liver were investigated using the enzyme-altered foci bioassay. The incidence of gamma-glutamyl transpeptidase (GGT)-positive foci was used as an early histochemical marker of putative preneoplastic hepatocytes. A single PO dose of trichloroethylene (490 mg/kg) was administered in corn oil to rats which had been partially hepatectomized 24 h previously. Three days following gavage with the chlorinated hydrocarbon the rats were promoted with an 8-week regimen of 500 ppm phenobarbital in drinking water. This protocol is known to induce enzyme-altered foci in the livers of animals which have received an initiating dose of a genotoxic carcinogen. Trichloroethylene was not found to induce GGT-positive foci under these conditions. Additionally, groups of rats were partially hepatectomized, initiated with N-nitrosodiethylamine (30 mg/kg; PO) and administered five times weekly doses of 200 mg trichloroethylene per rat in order to investigate the promoting activity of the chlorinated hydrocarbon in rat liver. No significant promoter effects were observed with trichloroethylene, although the results in this case were somewhat equivocal. The findings of these investigations are taken as partially supportive of an epigenetic, cytotoxic mechanism of tumorigenic action of trichloroethylene.

The initiating and promoting activities of 1,2-dibromoethane in rat liver were investigated using the enzyme-altered foci bioassay. The incidence of γ-glutamyl-transpeptidase (GGT)-positive foci was used as an early histochemical marker for hepatocarcinogenesis. To determine the initiating activity of 1,2-dibromoethane, the halogenated hydrocarbon was administered orally in corn oil as single or multiple doses (60 or 120 mg/kg) either before or after partial hepatectomy. The animals were then given a promoting regimen of 500 ppm phenobarbital in their drinking water. No increase in the incidence of GGT-positive foci was observed in any of the 1,2-dibromoethane initiation groups. The tumor promoting activity of 1,2-dibromoethane was determined in partially hepatectomized rats which were initiated with N-nitrosodiethylamine (30 mg/kg; po), and one week later were administered 1,2-dibromoethane (10 or 30 mg/kg) orally in corn oil five times weekly for 8 weeks. Control groups receiving sham hepatectomy or no initiator were also treated with the halogenated hydrocarbon five times weekly. Only in those animals which received partial hepatectomy, N-nitrosodiethylamine initiation, and 1,2-dibromoethane was the incidence of GGT-positive foci significantly increased. These results do not support significant initiator activity of 1,2-dibromoethane in rat liver, but do indicate that 1,2-dibromoethane possesses promoter activity which may contribute to its carcinogenic activity.

The antiepileptic drugs, phenobarbital and phenytoin, were determined in plasma by enzyme immunoassay (EMIT) and by high-pressure liquid chromatography (HPLC). In addition, the major metabolite of phenytoin, p-hydroxydiphenylhydantoin (HPPH), was determined by HPLC. Within-day and between-day coefficients of variation for both methods were 7.6% or less for phenobarbital and 8.7% or less for phenytoin, and for HPPH, by liquid chromatography, were 7.4% or less. Both methods also showed good linearity from subtherapeutic through low toxic concentrations. Comparison of the results of the two methods for phenobarbital and for phenytoin showed good correlations r = 0.99 and 0.97 respectively, indicating that HPLC can be used rather than the more commonly used EMIT. In addition, this HPLC method simultaneously measures both antiepileptic drugs and the unconjugated form of the major metabolite of phenytoin, and with prior hydrolysis, the conjugated form of p-hydroxydiphenylhydantoin.

In vivo and in vitro studies using [3H]glucosamine incorporation into prothrombin and into glycolipids were conducted in rat liver to determine the role of lipid-saccharides in the biosynthesis of prothrombin.