Biochemical microanalysis of glycogen content and glucose-6-phosphate dehydrogenase activity in focal lesions of the rat liver induced by N-nitrosomorpholine

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Abstract
Persisting focal lesions, namely glycogen storage (glycogenotic) foci and mixed cell foci, were induced in liver by treatment of rats with the hepatocarcinogen N-nitrosomorpholine in a concentration of 200 mg/l drinking water for 7 weeks. Four and seven weeks after withdrawal of the carcinogen, the persisting foci were dissected from freeze-dried cryostat sections and their glycogen content and glucose-6-phosphate dehydrogenase activity were analyzed with highly sensitive luminometrical tests. The foci composed exclusively of storage cells contained on an average 100% more glycogen than the surrounding tissue of normal appearance or the liver parenchyma of untreated control animals. The overall glycogen content of the mixed cell foci, which were composed of both glycogenotic and glycogen-poor basophilic cells, was not distinguishable from that of the normal liver tissue. The activity of the G6PDH showed a clear tendency to higher values in the majority of the small glycogen storage foci (up to 100 ng dissected material). However, in larger glycogenotic foci and in particular in the mixed cell foci the activity of this enzyme was significantly higher (by a factor of ∼3 and 6, respectively) than in the surrounding tissue of normal appearance and in the liver parenchyma of untreated controls. The data support the concept that hepatocarcinogens induce a focal hepatic glycogen storage disease of the liver which appears to elicit adaptive enzymatic changes gradually redirecting the disturbed carbohydrate metabolism towards other metabolic pathways, such as the pentose phosphate pathway.