This study investigates digestive and lysosomal
enzyme secretion of
azaserine-induced
pancreatic acinar carcinomas in response to
cholecystokinin in rats. After 15-20 months of treatment, 95% of the animals developed
pancreatic acinar carcinomas encompassing more than 90% of the tissue. In anesthetized rats basal
trypsin output was significantly elevated in the
tumor group despite diminished fluid secretion. There was a linear correlation between
tumor size and basal
amylase and
trypsin secretion.
Intravenous infusion of
cholecystokinin (25 IDU.kg-1.h-1) induced a significantly lower secretion of fluid per gram pancreas, as well as decreased
amylase and
trypsin output, in the
tumor group compared with the control group. Plasma
amylase and
lipase levels were significantly elevated in the
tumor group under both basal and stimulated conditions. The output of the lysosomal
enzymes beta-D-
glucuronidase and alpha-D-
glucosidase was significantly increased in the
tumor group under background
secretin infusion. Additional
cholecystokinin infusion caused a sharp increase in
glucuronidase output in this group with only minimal increase in controls.
Glucosidase output increased similarly in both groups.
Amylase,
lipase, and
trypsin tumor tissue concentrations were markedly reduced by 85%, 90%, and 87%, respectively. It was concluded that the decreased secretory response of digestive
enzymes may result from decreased synthesis, lowered storage capabilities, and/or a decreased/increased responsiveness to
cholecystokinin. Increased
glucuronidase secretion may reflect an augmented cell turnover of malignant tissue.