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
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 11β 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.