title: The INK4a /ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident.
abstract: Previous studies have shown that during the period subsequent to the Chernobyl accident, increases in morbidity, aggressivity and proliferative activity of renal-cell carcinomas (RCCs) in Ukrainian patients were recognized. The present paper describes the molecular alterations of those tumor suppressor genes located on chromosome 9p21 ( INK4a/ARF locus and p15(INK4B)) in 26 primary renal-cell epithelial tumors from patients with different degrees of radiation exposure after the Chernobyl accident in Ukraine. Radiometric measurement of Cesium 137 ((137)Cs) was conducted with 1-day urine from all patients before surgery. Our results demonstrate that RCCs from patients living in the radio-contaminated areas showed aberrant hypermethylation of p14(ARF) and p16(INK4A) genes, associated with increased p38MAPK, p14(ARF), mdm2, cyclinD1 and Ki67 protein expression levels. Present findings show the possibility that chronic long-term low-dose radiation activates the INK4a/ARF locus, targeted by activation of the p38MAPK cascade. These actions could lead to disruptions and loss of cell cycle checkpoints and, thereby, to cellular transformation.
authors.affiliation: Department of Pathology, Institute of Urology, Academy of Medical Sciences of Ukraine, 9(a) Yu. Kotzubinsky, 04053 Kiev, Ukraine.
authors.forename: Alina
authors.initials: A
authors.lastname: Romanenko
authors.forename: Luisa
authors.initials: L
authors.lastname: Morell-Quadreny
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Lopez-Guerrero
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellin
authors.forename: Valentin
authors.initials: V
authors.lastname: Nepomnyaschy
authors.forename: Alexander
authors.initials: A
authors.lastname: Vozianov
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Bosch
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects*; D002587:Cesium Isotopes / Q000652:urine; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000528:radiation effects; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16 / Q000528:radiation effects*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000528:radiation effects; D014455:Ukraine; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002587:Cesium Isotopes; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF; D048051:p38 Mitogen-Activated Protein Kinases