Enhanced proliferation of acinar and progenitor cells by prophylactic pilocarpine treatment underlies the observed amelioration of radiation injury to parotid glands.
BACKGROUND
Administration of pilocarpine before irradiation can ameliorate radiation-induced hyposalivation. Indirect evidence suggests that this effect may be mediated through induction of a compensatory response. In this study, this hypothesis is tested directly, by assessing the proliferation of progenitor and secretory cells in irradiated and non-irradiated parotid gland tissue.


METHODS
In a rat model, parotid glands were unilaterally irradiated with a single dose of 15 Gy, 60 min after administration of pilocarpine (4.0mg/kg). Rats were sacrificed for proliferating cell nuclear antigen (PCNA) labelling, assessing the number of proliferating progenitor and secretory cells, before, and 10h, 1, 3, 7, 10, 20 and 30 days after irradiation.


RESULTS
A small radiation-induced increase in PCNA expressing cells was observed, both in the acinar (secretory cells) and intercalated duct cell (containing the progenitor cells) compartment. This increment was significantly enhanced in pilocarpine pre-treated glands. In fact, in this group of animals increased proliferation was observed both in the irradiated and the shielded gland.


CONCLUSIONS
Amelioration of early loss of rat salivary gland function after radiation by pilocarpine pre-treatment is, at least in part, due to compensatory mechanisms through increased proliferation of undamaged cells.
Burlage
Fred R
FR
Department of Radiation Oncology, University Medical Center Groningen, The Netherlands. f.r.burlage@rt.umcg.nl
Faber
Hette
H
Kampinga
Harm H
HH
Langendijk
Johannes A
JA
Vissink
Arjan
A
Coppes
Rob P
RP
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D010862:Pilocarpine / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects
D018721:Muscarinic Agonists; D018809:Proliferating Cell Nuclear Antigen; D010862:Pilocarpine