EFFECTS OF CYCLIC-AMP ON GROWTH AND DIFFERENTIATION OF RAT RETINOBLASTOMA-LIKE TUMOR-CELLS INVITRO

  • 1 January 1982
    • journal article
    • research article
    • Vol. 22  (2) , 145-156
Abstract
The effects of cAMP on the growth and differentiation of RAO 188 cells, a cultured cell line derived from a retinoblastoma-like tumor induced in an inbred rat by intravitreous inoculation with human adenovirus serotype 12 were examined. After adding cAMP analogs (dibutyryl cAMP and 8-bromo cAMP) and phosphodiesterase inhibitors (theophylline, aminophylline, and 1-methyl-3-isobutyl xanthine) to the RAO 188 cell culture medium, changes in cell incorporation of the DNA and RNA precursors 14C-thymidine and 3H-uridine. The morphologic alterations of RAO 188 by phase-contrast and transmission and scanning electron microscopy were observed. Incorporation of the labeled precursors decreased with increased concentrations of cAMP analogs and phosphodiesterase inhibitors. Incorporation of the labeled precurors was inhibited shortly after the addition of dibutyryl cAMP to the culture medium. The effect was maximal at 8 h and was sustained for up to 48 h. Reversibility of cAMP effects on incorporation gradually decreased for 10 days; at 10 days these effects were essentially irreversible. Neuritelike processes developed shortly after cAMP analog treatment and formed a network after 24 h. Transmission electron microscopy disclosed changes in the cell membrane and cytoplasm of cells treated with 8-bromo cAMP and theophylline:perturbation of the cell membrane and the appearance of intercellular junctional devices and microfilaments. The activity of glutamate decarboxylase, which is involved in the biosynthesis of .gamma.-aminobutyric acid, was increased in treated cells. Apparently, cAMP decreases DNA and RNA synthesis and cell proliferation and facilitates morphologic and biochemical differentiation of RAO 188 cells.

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