The studies presented here are designed to; (i) identify the molecular mechanisms involved in beta-adrenergic receptor (beta-AR) stimulation induced salivary gland hyperplasia and gene expression; (ii) examine the effect(s) of irradiation on early response genes encoding transcription factors (c-fos, c-jun, jun B), parotid gland genes, proline rich proteins (PRP), salivary gland function and morphology; (iii) characterize the kinetics of expression of c-fos, c-jun, jun B and glandular genes during rat parotid gland development and differentiation; (iv) determine the expression of c-fos, c-jun and jun B genes after different stimuli and during the cell cycle, in a salivary cell line (A5); understand salivary epithelial cell: basement membrane interactions. During this reporting period we have demonstrated that; (1) a single dose (15Gy) of ionizing radiation diminishes parotid gland weight and saliva output and prolongs the expression of c-fos, c-jun, jun B. The combination of irradiation and isoproterenol has a profound effect on c-jun expression. Irradiation has no effect on parotid saliva composition or PRP gene expression; (2) PRP and amylase genes and proteins are undetectable at the early states of parotid gland development and increase with age after 7 days; (3) c-fos and c-jun genes and proteins are highly expressed during both parotid gland proliferation (20 day in utero) and differentiation (7, 14, 21, 28 days); (4) c-fos and jun B mRNAs are elevated at the early phases of the A5 cell cycle and are inducable by isoproterenol at different stages of the cycle; (5) in A5 cells there is a differential expression between c- fos and c-jun and jun B after incubation with the Ca++ ionophore A23187; and (6) culture of HSG salivary epithelial cells or reconstituted basement membrane induces morphogenesis.
