Abstract
Comparative studies of enzyme activities during the dedifferentiation of hepatic cells and through their development into overt hepatomas are few and contradictory. This study was designed to investigate the histochemical, biochemical and morphologic features of the altered liver cells with particular emphasis on the importance and validity of the histoenzymatic behavior of glucose-6-phosphatase (G6Pase) as a marker for the detection of precancerous hepatic cells. Serum and hepatic levels of G6Pase were analyzed and compared with the histoenzymatic behavior of this enzyme. The use of other enzymes, such as adenosine triphosphatase (ATPase) and gamma glutamyl-transpeptidase (GGT) as histochemical markers for malignancy was also tested. The activities of a variety of enzymes commonly used as diagnostic tools were also evaluated in both the liver homogenates and sera of rats treated with 2 mg diethylnitrosamine (DENA)/kg body weight for 2-28 weeks. Using G6Pase as a histoenzymatic marker, precancerous cells appeared after 4 weeks of exposure to DENA in the form of small islets devoid of G6Pase activity. These G6Pase free cells increased in number forming larger islands and finally appeared as tumor nodules after 28 weeks of treatment. The histoenzymatic behavior of ATPase was identical to that of G6Pase. The precancerous cells, as well as the tumor cells appeared devoid of ATPase activity. The application of GGT as a marker, showed significantly increased activity in the altered liver and tumor cells. Increased serum levels of G6Pase were noted after 10 weeks and were greatly elevated in the late stages of the evolution of the precancerous cells. After 14 weeks of DENA administration, the hepatic G6Pase activity was depressed and greatly diminished as the size and number of these foci increased. In animals bearing hepatomas, the G6Pase levels were markedly decreased in both the sera and liver homogenates and totally lacking in the tumor cells. Data obtained from the evaluation of sera and hepatic activities of acid and alkaline phosphatases, aspartate and alanine aminotransferases, and lactic and isocritic dehydrogenases were inconclusive as compared to G6Pase.