Abstract
The feasibility of using biochemical assays of gamma-glutamyltranspeptidase (gamma-GTP) and N-hydroxy-N-2-fluorenylacetamide sulfotransferase (N-OH-2-FAA ST) activities to monitor the effects of treatment of male Sprague-Dawley rats with a two-stage hepatocarcinogenic regimen was investigated. One week after initiation with diethylnitrosamine (200 mg/kg of bw), the rats were treated with 10 oral doses within 2 weeks of N-2-fluorenylacetamide (2-FAA) at 0.05 mmole/kg or vehicle (corn oil) at 5 ml/kg of body weight. After five doses of 2-FAA or corn oil, half of the rats in each group underwent partial (70%) hepatectomy (PH). Three days after completion of 2-FAA treatment, gamma-GTP activity increased approximately 8-fold in the livers of both the nonhepatectomized (-PH) and hepatectomized (+PH) groups. After 17 days, the enzyme activity decreased to the control level in the -PH group but increased 3.1-fold above the control level in the +PH group. After 31, 66, and 87 days, gamma-GTP activity increased only 1.4- to 2.6-fold in the -PH group, whereas that of +PH group increased 15- to 32-fold. N-OH-2-FAA ST activity, determined 3 days after completion of 2-FAA treatment, decreased by approximately 60% in the -PH and +PH groups. After 17 days, the effect of PH became evident in that the losses of N-OH-2-FAA ST activity were smaller (20%) in the -PH than in the +PH group (45.5%). After 31, 66, and 87 days, the respective decreases of 27, 29, and 41% in the +PH group were significant. Nodules excised from the livers of the +PH group 87 days after treatment with 2-FAA showed 25% of N-OH-2-FAA ST activity of the control livers. The data suggested that early increases in gamma-GTP and decreases in N-OH-2-FAA ST activities, which were independent of PH, were affected by hepatic metabolism of 2-FAA. After 17 days, the presumed clearance of 2-FAA, the effect of PH was manifested in that it prevented return to control levels of both enzyme activities in 2-FAA-treated rats. The time and PH dependency of the extent of modulations of gamma-GTP and N-OH-2-FAA ST activities support their assays as markers of the promotion/progression of hepatocarcinogenesis.