title: Salivary gland-sparing prophylactic pilocarpine treatment has no effect on tumor regrowth after irradiation.
abstract: Radiotherapy of head and neck cancer frequently damages the salivary glands. Prophylactic administration of the muscarinic receptor agonist pilocarpine reduces subsequent radiation damage to the salivary glands in rats, but its effects on tumor cell radiosensitivity and tumor regrowth after irradiation had not been assessed. In the current study, we first tested the effect of pilocarpine on clonogenic cell survival in vitro. No effect of pilocarpine on radiosensitivity was observed in a panel of cell lines either with or without expression of muscarinic receptors. Second, a single dose of pilocarpine known to protect salivary gland tissue from radiation damage was given to rats transplanted with subcutaneously growing rhabdomyosarcomas 1 h prior to irradiation with a single dose of 35 Gy. No alterations in growth delay were detected (26 +/- 2 days for controls compared to 26 +/- 2 days for pilocarpine treatment). Our data indicate that pilocarpine pretreatment, which has been shown previously to protect salivary glands from radiation, does not protect tumor cells or tumors. Use of this drug therefore may lead to therapeutic gain in the treatment of head and neck cancer.
authors.affiliation: Department of Radiation and Stress Cell Biology, University of Groningen, 9713 AV Groningen, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Licht
authors.forename: H H
authors.initials: HH
authors.lastname: Kampinga
authors.forename: R P
authors.initials: RP
authors.lastname: Coppes
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010862:Pilocarpine / Q000494:pharmacology*; D011832:Radiation Injuries / Q000517:prevention & control; D051381:Rats; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000473:pathology / Q000532:radiotherapy*; D012468:Salivary Gland Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D012469:Salivary Glands / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D018721:Muscarinic Agonists; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; D010862:Pilocarpine