title: DNA-flow cytometry, DNA-image cytometry and proliferation index (MIB-5) in irradiated rat salivary glands and salivary gland tumors.
abstract: OBJECTIVE
  Salivary glands (SG) can become atrophic following radiation exposure. Malignant transformation of SG in a radiation field is another known sequela of patients who have been treated by radiotherapy for a malignant tumor in the head and neck region. The aim of this study was to investigate cytogenetic alterations and to determine the proliferation index (PI) of SG of rats subjected to various total dosages of fractionated X-rays.
  
  
  METHODS
  We investigated rat SG, subjected to 20, 40, or 60 Gy exposure by X-rays to the left neck and skull base. Non-irradiated rats served as a control group. Tumors originating from the SG were histologically-diagnosed following the descriptions for human SG tumors. The MIB-5 antibody was used to determine the PI. The ploidy was determined by flow and image cytometry (FCM, ICM).
  
  
  RESULTS
  We consistently recorded diploid histograms in the FCM in irradiated glands. ICM revealed aneuploid histograms in 6/22 tumors, 3 of them were Auer Type III or IV. The PI showed a dose- and time-dependent course, indicative of variable regeneration properties of the parenchyma. Statistically significant differences were found for the PI within the irradiation groups and comparing irradiated SG and tumors.
  
  
  CONCLUSIONS
  Irradiation of rat SG can cause almost complete loss of function. On the other hand, the PI remained in animals subjected to 40 Gy and investigated 1 year after completion of radiation at a level up to 10-fold higher than in untreated controls. The PI in carcinoma is higher in this species than in irradiated SG. Constantly elevated PI could support the development of cancer in SG.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Eppendorf University Hospital, University of Hamburg, Germany. rfriedri@uke.uni-hamburg.de
authors.forename: R E
authors.initials: RE
authors.lastname: Friedrich
authors.forename: N
authors.initials: N
authors.lastname: Hieke
authors.forename: C
authors.initials: C
authors.lastname: Stern
authors.forename: C
authors.initials: C
authors.lastname: Lautenschläger
authors.forename: H J
authors.initials: HJ
authors.lastname: Holzhausen
authors.forename: J
authors.initials: J
authors.lastname: Caselitz
authors.forename: S
authors.initials: S
authors.lastname: Bartel-Friedrich
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000782:Aneuploidy; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics / Q000473:pathology; D002455:Cell Division; D004273:DNA, Neoplasm / Q000032:analysis / Q000528:radiation effects*; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D019044:Image Cytometry / Q000379:methods*; D019394:Ki-67 Antigen / Q000378:metabolism; D011833:Radiation Injuries, Experimental; D051381:Rats; D017208:Rats, Wistar; D012468:Salivary Gland Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*
chemical_list: D004273:DNA, Neoplasm; D019394:Ki-67 Antigen