In an attempt to find an explanation for the increasing hypoglycaemia observed during DAB-induced cancer invasion of hepatic tissue, we measured the activities of key enzymes of the Embden-Meyerhof pathway-i.e. glucokinase, phosphofructokinase, and pyrubate kinase. All these activities diminished in absolute terms.A comparison of glucokinase and phosphofructokinase activities, on the one hand, with those of glucose-6-phosphatase and fructose-l,6-diphosphatase, on the other, revealed that glucide breakdoan progressively outstrips glucide formation during cancer invasion.Furthermore, a larger proportion of the glucides makes use of the pentose phosphate pathway. The significance of this finding is discussed.Au cours de nos recherches, l'hypoglycemie nous est apparue conime une caracteristique de I'animal porteur d'hepatome (Jacob, 1967), et il nous a semble interessant de rechercher les raisons de cette anomalie.Parmi les diverses causes de ce dereglement, nous avons envisage I'utilisation accrue du glucose pour faire face aux besoins Cnergetiques de la cellule, ce qui se traduit par une plus grande activite de la voie Embden-Meyerhof. On sait en effet depuis Warburg et Minami (1923) que la formation d'acide lactique est plus &levee dans les cellules cancereuses que dans les cellules nor-males; toutefois I'augmentation de ce seul metabolite ne saurait Ctre confondu avec une stirnulation de la voie glycolytique. En effet, I'acide pyruvique dont provient I'acide lactique a de nombreuses utilisations dans la cellule; il peut, apres transformation en acetyl CoA, Ctre utilisk pour le cycle de Krebs ou pour la synthese des lipides; la diminution de l'une ou I'autre de ces voies peut donc entrainer une plus forte production de I'acide lactique pour une mCme quantite d'acide pyruvique forme, c'est-a-dire pour une mCme activite des enzymes de la voie Embden-Meyerhof.

MODlFICATIONS OF CARBOHYDRATE METABOLISM OBSERVED DURING HEPATOCARCINOGENESIS INDUCED BY DAB. ' STUDIES O N GLYCOGEN METABOLISMI n an attempt 10 find an explanation for the hypoglycaeinia observed in rats with DAB-induced hepatomas, we studied glycogen metabolism in rat livers in which cancer invasion proceeded at different speeds.We measured the content of glycogen and ojglucose-6-phosphate in the liver and determined the activities of glycogen-syiithrtase, phosphorylase, and phosphoglucomutase.We demonstrated that the cause of the hypoglycaemia varies froin one case to another. I n some instances, glycogen accumulates in the liver but can no longer be broken down into glucose, wrhile in others glycogen is no longer synthesized.

MODIFICATIONS OF CARBOHYDRATE METABOLISM OBSERVED DURING HEPATOCARCINOGENESIS BY DAB l. STUDIES ON PENTOSE PHOSPHATE PATHWAYIn an attempt to find an explanation for the hypoglycaemia observed in rats during DA B-induced cancer invasion of hepatic tissue, we studied the pentose phosphate pathway. The amount of G6P entering into this pathway increases in precancerous and cancerous hepatic tissue on account of the increase of glucose-6-phosphate dehydrogrnase activity. The activity of 6-phosphogluconate dehydrogenase is decreased, and a part of the 6-phosphogluconate is retired from the shunt pathway. This can be one of the causes of hypoglycaemia. The metabolism of ribose-5-phosphate in the pentose phosphate pathway is not modified by the carcinogenesis.