title: Continuous and low-energy 125I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth.
abstract: BACKGROUND
  Iodine 125 (125I) seed irradiation is an effective treatment for unresectable pancreatic cancers. However, the radiobiological mechanisms underlying brachytherapy remain unclear. Therefore, we investigated the influence of continuous and low-energy 125I irradiation on apoptosis, expression of DNA methyltransferases (DNMTs) and cell growth in pancreatic cancers.
  
  
  METHODS
  For in vitro 125I seed irradiation, SW-1990 cells were divided into three groups: control (0 Gy), 2 Gy, and 4 Gy. To create an animal model of pancreatic cancer, the SW 1990 cells were surgically implanted into the mouse pancreas. At 10 d post-implantation, the 30 mice with pancreatic cancer underwent 125I seed implantation and were separated into three groups: 0 Gy, 2 Gy, and 4 Gy group. At 48 or 72 h after irradiation, apoptosis was detected by flow cytometry; changes in DNMTs mRNA and protein expression were assessed by real-time PCR and western blotting analysis, respectively. At 28 d after 125I seed implantation, in vivo apoptosis was evaluated with TUNEL staining, while DNMTs protein expression was detected with immunohistochemical staining. The tumor volume was measured 0 and 28 d after 125I seed implantation.
  
  
  RESULTS
  125I seed irradiation induced significant apoptosis, especially at 4 Gy. DNMT1 and DNMT3b mRNA and protein expression were substantially higher in the 2 Gy group than in the control group. Conversely, the 4 Gy cell group exhibited significantly decreased DNMT3b mRNA and protein expression relative to the control group. There were substantially more TUNEL positive in the 125I seed implantation treatment group than in the control group, especially at 4 Gy. The 4 Gy seed implantation group showed weaker staining for DNMT1 and DNMT3b protein relative to the control group. Consequently, 125I seed implantation inhibited cancer growth and reduced cancer volume.
  
  
  CONCLUSIONS
  125I seed implantation kills pancreatic cancer cells, especially at 4 Gy. 125I-induced apoptosis and changes in DNMT1 and DNMT3b expression suggest potential mechanisms underlying effective brachytherapy.
authors: Department of Gastroenterology, The Changhai Hospital, The Second Military Medical University, Shanghai, PR China.
authors: Jian-xia
authors: JX
authors: Ma
authors: Zhen-dong
authors: ZD
authors: Jin
authors: Pei-ren
authors: PR
authors: Si
authors: Yan
authors: Y
authors: Liu
authors: Zheng
authors: Z
authors: Lu
authors: Hong-yu
authors: HY
authors: Wu
authors: Xue
authors: X
authors: Pan
authors: Luo-wei
authors: LW
authors: Wang
authors: Yan-fang
authors: YF
authors: Gong
authors: Jun
authors: J
authors: Gao
authors: Li
authors: L
authors: Zhao-shen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse