Different proliferative responsiveness of fibroblasts and mesothelial cells in the rat mesentery following administration of compound 48/80 at various hours of the day.

The proliferative responsiveness of fibrolasts and mesothelial cells in the mesenterial membrane of normal rats was studied quantitatively after a single i.p. injection of the mast-cell activating and histamine-releasing drug Compound 48/80. To make some allowance for a possible chronobiologic effect of the circadian type on the induced proliferation, the drug was given at 1 a.m., 9 a.m., or 5 p.m., and the animals were examined 16, 24, and 32 h later. The proliferation was estimated by cytophotometric Feulgen DNA measurements in individual fibroblast and mesothelial cell nuclei, and by mitotic frequency counting. The main result was that a larger fraction of fibroblasts than of mesothelial cells was stimulated to proliferation, regardless of the hour of treatment with Compound 48/80. It was further demonstrated that in control animals the fraction of cells of either fibroblastic or mesothelial type present in the S cum G2 cell-cycle phases varied markedly at different hours of the day. Quantitative differences appeared in the induced proliferation with regard to the hour of treatment. The most vigorous proliferative response appeared after administration of the drug at 9 a.m. The fraction of cells in the S cum G2 cell-cycle phases was then increased at 16 h and the fraction of dividing cells at 24 h after treatment, illustrating the promptness of the induced proliferative reaction.