Your browser doesn't support javascript.
loading
Time-matched analysis of DNA adduct formation and early gene expression as predictive tool for renal carcinogenesis in methylazoxymethanol acetate treated Eker rats.
Klaus, Valentina; Bastek, Heinke; Damme, Katja; Collins, Leonard B; Frötschl, Roland; Benda, Norbert; Lutter, Dominik; Ellinger-Ziegelbauer, Heidrun; Swenberg, James A; Dietrich, Daniel R; Stemmer, Kerstin.
Afiliación
  • Klaus V; Computational Discovery Research, Institute for Diabetes and Obesity, Helmholtz Diabetes Center & German Center for Diabetes Research (DZD), Helmholtz Zentrum München, Neuherberg, Germany.
  • Bastek H; Human and Environmental Toxicology, University of Konstanz, Konstanz, Germany.
  • Damme K; Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
  • Collins LB; Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
  • Frötschl R; Federal Institute for Drugs and Medical Devices, Bonn, Germany.
  • Benda N; Federal Institute for Drugs and Medical Devices, Bonn, Germany.
  • Lutter D; Computational Discovery Research, Institute for Diabetes and Obesity, Helmholtz Diabetes Center & German Center for Diabetes Research (DZD), Helmholtz Zentrum München, Neuherberg, Germany.
  • Ellinger-Ziegelbauer H; Investigational Toxicology, DD-ED-Toxicology, Bayer AG, Wuppertal, Germany.
  • Swenberg JA; Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
  • Dietrich DR; Human and Environmental Toxicology, University of Konstanz, Konstanz, Germany.
  • Stemmer K; Metabolism and Cancer, Institute for Diabetes and Obesity, Helmholtz Diabetes Center & German Center for Diabetes Research (DZD), Helmholtz Zentrum München, Neuherberg, Germany. kerstin.stemmer@helmholtz-muenchen.de.
Arch Toxicol ; 91(10): 3427-3438, 2017 Oct.
Article en En | MEDLINE | ID: mdl-28349193
Genotoxic carcinogens pose great hazard to human health. Uncertainty of current risk assessment strategies and long latency periods between first carcinogen exposure and diagnosis of tumors have raised interest in predictive biomarkers. Initial DNA adduct formation is a necessary step for genotoxin induced carcinogenesis. However, as DNA adducts not always translate into tumorigenesis, their predictive value is limited. Here we hypothesize that the combined analysis of pro-mutagenic DNA adducts along with time-matched gene expression changes could serve as a superior prediction tool for genotoxic carcinogenesis. Eker rats, heterozygous for the tuberous sclerosis (Tsc2) tumor suppressor gene and thus highly susceptible towards genotoxic renal carcinogens, were continuously treated with the DNA alkylating carcinogen methylazoxymethanol acetate (MAMAc). Two weeks of MAMAc treatment resulted in a time-dependent increase of O6-methylguanine and N7-methylguanine adducts in the kidney cortex, which was however not reflected by significant expression changes of cyto-protective genes involved in DNA repair, cell cycle arrest or apoptosis. Instead, we found a transcriptional regulation of genes involved in the tumor-related MAPK, FoxO and TGF-beta pathways. Continuous MAMAc treatment for up to 6 months resulted in a mild but significant increase of cancerous lesions. In summary, the combined analysis of DNA adducts and early gene expression changes could serve as a suitable predictive tool for genotoxicant-induced carcinogenesis.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetato de Metilazoximetanol / Aductos de ADN / Riñón Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Arch Toxicol Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetato de Metilazoximetanol / Aductos de ADN / Riñón Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Arch Toxicol Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania