| Summary: | The mechanism by which drug-induced salivary gland enlargement occurs clinically is not known. Denervation experiments suggest a direct cellular action of the relevant compounds in the presence of intact cell receptors. The denervated gland enlarges in vivo in response to exogenous isoprena1ine. Since the salivary glands produce cell growth factors a complex series of events may be involved. Target cells for neurotransmitter action and for growth factor production have not been isolated. This thesis describes an alternative approach to understanding druginduced salivary gland enlargement. By using cultured cells the aim was to isolate the sal ivary eel Is from the complexities of in vivo control . However, it was first necessary to define the culture requirements of the three major murine and human labial salivary glands. Conditions were designed to optimise growth from primary explant cultures and to facilitate identification of cells in the outgrowth. An optimum medium composition was established for growth of salivary gland cells on different substrata. The cells remain viable by Trypan Blue exclusion and can be serially propagated. Cell identification was by morphology, u1trastrueture, histochemica1 criteria and by eel 1-directed antibodies. Electron micrography confirmed that some of the cultured cells were epithelial in character. By light microscopy cell morphology bore an inconstant relationship to other markers for ductal epithelial cells. Similar proportions of cells react positively for 113 hydroxysteroid dehydrogenase and with salivary duct antibody. Either criterion appears to quantify the proportion of ductal epithelial cells in a mixed culture. Quantification of the cells growing from human salivary explants was also attempted. Ductal cells convert Cortisol to cortisone but there was no direct relationship observed between 11? hydroxysteroid dehydrogenase and the metabolism of Cortisol. The main conclusions are that human and murine salivary gland cells can be propagated in vitro for prolonged periods and that a proportion of these cells are ductal in origin. Isoprenaline in a wide range of concentrations in vitro did not sufficiently alter the salivary cell growth patterns to account for gland enlargement in vivo. Other neurotransmitters even at high concentrations produced no increase in culture growth. Under these circumstances all neurotransmitters, except isoprenaline, altered the proportion of ductal cells present.
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