Enhancement of R3230AC Rat Mammary Tumor Growth and Cellular Differentiation by Dibutyryl Cyclic Adenosine Monophosphate23

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Abstract
Dally 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 R3230AC 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. Injectlons of 17 β-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 electrondense granules resembling protein. DBcAMP-treated tumor cells were marked by a proliferation of the Golgi complex and numerous vesicles containing fine granular material.