Daily sc
injections of 8 mg N6, O2'-dibutyryl 3',5'-cyclic
AMP (
DBcAMP) beginning 1 day after
tumor implantation significantly increased the growth rate of R32230AC rat mammary
adenocarcinomas, which nearly doubled in in situ volume by day 40 compared to similarly implanted
tumors in saline-injected controls. Weights of excised
tumors, intact, drained, and dried all increased approximately 80%, which suggested that the increase in
tumor size was not due to accumulation of secreted fluid or tissue water.
Injections of 17beta-estradiol
valerate (0.1 mg/wk) from day 1 or of
DBcAMP from day 22 resulted in insignificant changes in growth--28% and 35% increases in
tumor volume and a 5% decrease and an 18% increase, respectively, in drained wet weight. Electron microscopic examination revealed that
estrogen and
DBcAMP caused differentiation of the
tumor cells into two different states:
Estrogen-treated
tumors resembled lactating mammary glands; they contained large lipid droplets, organized rough endoplasmic reticulum, and vesicles containing electron dense granules resembling
protein.
DBcAMP-treated
tumor cells were marked by a proliferation of the Golgi complex and numerous vesicles containing fine granular material.