FURTHER STUDIES ON THE RELATIONSHIP BETWEEN DRUG‐INDUCED MAST‐CELL SECRETION AND LOCAL CELL PROLIFERATION

Abstract

A single i.p. injection of Compound 48/80 [p-methoxyphenethylmethylamine formaldehyde product] in rats causes mast cell activation which is followed by a proliferation in fibroblasts and mesothelial cells in the mesentery. The same is true of organ-cultured rat mesentery, but in cultured guinea pig mesentery Compound 48/80 has no morphological effects on mast cells and does not induce proliferation. The relationship between mast-cell secretion and cell proliferation in surrounding cells was studied. Proliferation was estimated by cytophotometric Feulgen DNA measurements in individual fibroblast and mesothelial cell nuclei; by measurements of incorporation of 3H-TdR [thymidine] into DNA; and by estimation of mitotic frequency. Mast-cell secretion was studied morphologically and by biochemical quantitation of histamine release. Compound 48/80 is a potent mast cell activator in the rat, stimulating mast cells to secretion. Polymyxin B, another powerful mast-cell activator, apparently chemically unrelated to Compound 48/80, stimulates the mesenterial cells to proliferation in the rat. In the guinea pig Compound 48/80 does not induce mast-cell secretion or proliferation in fibroblasts and mesothelial cells in the mesentery. Cell proliferation induced by Compound 48/80 and Polymyxin B in rat mesentery is causally related to mast-cell secretion.