title: Radiation-induced gastric epithelial apoptosis occurs in the proliferative zone and is regulated by p53, bak, bax, and bcl-2.
abstract: Unlike the small intestine and colon where gamma-radiation-induced apoptosis has previously been well characterized, the response of murine gastric epithelium to gamma-radiation has not been investigated in detail. Apoptosis was therefore assessed on a cell positional basis in gastric antral and corpus glands from adult male mice following gamma-radiation. Maximum numbers of apoptotic cells were observed in both antrum and corpus at 48 h and at radiation doses greater than 12 Gy. However, the number of apoptotic cells observed in the gastric epithelium was much lower than observed in the small intestine or colon after similar doses of radiation. Hematoxylin and eosin, caspase 3 immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling detected similar numbers and cell positional distributions of apoptotic cells, hence hematoxylin and eosin was used for subsequent studies. The highest numbers of apoptotic cells were observed at cell positions 5-6 in the antrum and cell positions 15-18 in the corpus. These distributions coincided with the distributions of PCNA-labeled proliferating cells, but not with the distributions of H(+)-K(+)-ATPase-labeled parietal cells or TFF2-labeled mucous neck cells. Decreased numbers of apoptotic gastric epithelial cells were observed in p53-null, bak-null, and bax-null mice compared with wild-type counterparts 6 and 48 h after 12 Gy gamma-radiation. Significantly increased numbers of apoptotic gastric epithelial cells were observed in bcl-2-null mice compared with wild-type littermates 6 h after 12 Gy gamma-radiation. Radiation therefore induces apoptosis in the proliferative zone of mouse gastric epithelium. This response is regulated by the expression of p53, bak, bax, and bcl-2.
authors.affiliation: Division of Gastroenterology, School of Clinical Sciences, Univ of Liverpool, Liverpool, UK.
authors.forename: S M C
authors.initials: SM
authors.lastname: Przemeck
authors.forename: C A
authors.initials: CA
authors.lastname: Duckworth
authors.forename: D M
authors.initials: DM
authors.lastname: Pritchard
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000528:radiation effects; D004848:Epithelium / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D005720:Gamma Rays; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D017506:H(+)-K(+)-Exchanging ATPase; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009077:Mucins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D011706:Pyloric Antrum / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D013270:Stomach / Q000473:pathology / Q000528:radiation effects; D000071164:Trefoil Factor-2; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics*; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C481546:TFF2 protein, mouse; D000071164:Trefoil Factor-2; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D017506:H(+)-K(+)-Exchanging ATPase