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Animal model for age- and sex-related genotoxicity of diethylstilbestrol
Fučić, A; Stojkovic, R; Katić, J; Markovic, D; Ferencic, Z; Korsić, M; Jazbec, A. M; Gamulin, M.
  • Fučić, A; Institute for Medical Research and Occupational Health. Zagreb. HR
  • Stojkovic, R; Ruđer Bosković Institute. Division of Molecular Medicine. Zagreb. HR
  • Katić, J; Institute for Medical Research and Occupational Health. Zagreb. HR
  • Markovic, D; GlaxoSmithKline Research Centre Zagreb Ltd. Zagreb. HR
  • Ferencic, Z; Children's Hospital "Srebrnjak". HR
  • Korsić, M; University Hospital Zagreb. Zagreb. HR
  • Jazbec, A. M; University of Zagreb. Faculty of Forestry. Zagreb. HR
  • Gamulin, M; University Hospital Zagreb. Zagreb. HR
Braz. j. med. biol. res ; 42(11): 1090-1096, Nov. 2009. ilus, tab
Artigo em Inglês | LILACS | ID: lil-529108
ABSTRACT
Environmental xenoestrogens pose a significant health risk for all living organisms. There is growing evidence concerning the different susceptibility to xenoestrogens of developing and adult organisms, but little is known about their genotoxicity in pre-pubertal mammals. In the present study, we developed an animal model to test the sex- and age-specific genotoxicity of the synthetic estrogen diethylstilbestrol (DES) on the reticulocytes of 3-week-old pre-pubertal and 12-week-old adult BALB/CJ mice using the in vivo micronucleus (MN) assay. DES was administered intraperitoneally at doses of 0.05, 0.5, and 5 µg/kg for 3 days and animals were sampled 48, 72 and 96 h, and 2 weeks after exposure. Five animals were analyzed for each dose, sex, and age group. After the DES dose of 0.05 µg/kg, pre-pubertal mice showed a significant increase in MN frequency (P < 0.001), while adults continued to show reference values (5.3 vs 1.0 MN/1000 reticulocytes). At doses of 0.5 and 5 µg/kg, MN frequency significantly increased in both age groups. In pre-pubertal male animals, MN frequency remained above reference values for 2 weeks after exposure. Our animal model for pre-pubertal genotoxicity assessment using the in vivo MN assay proved to be sensitive enough to distinguish age and sex differences in genome damage caused by DES. This synthetic estrogen was found to be more genotoxic in pre-pubertal mice, males in particular. Our results are relevant for future investigations and the preparation of legislation for drugs and environmentally emitted agents, which should incorporate specific age and gender susceptibility.
Assuntos

Texto completo: DisponíveL Índice: LILACS (Américas) Assunto principal: Reticulócitos / Carcinógenos / Modelos Animais / Dietilestilbestrol Tipo de estudo: Estudo prognóstico Limite: Animais Idioma: Inglês Revista: Braz. j. med. biol. res Assunto da revista: Biologia / Medicina Ano de publicação: 2009 Tipo de documento: Artigo País de afiliação: Croácia Instituição/País de afiliação: Children's Hospital "Srebrnjak"/HR / GlaxoSmithKline Research Centre Zagreb Ltd/HR / Institute for Medical Research and Occupational Health/HR / Ru&#273;er Boskovi&#263; Institute/HR / University Hospital Zagreb/HR / University of Zagreb/HR

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Texto completo: DisponíveL Índice: LILACS (Américas) Assunto principal: Reticulócitos / Carcinógenos / Modelos Animais / Dietilestilbestrol Tipo de estudo: Estudo prognóstico Limite: Animais Idioma: Inglês Revista: Braz. j. med. biol. res Assunto da revista: Biologia / Medicina Ano de publicação: 2009 Tipo de documento: Artigo País de afiliação: Croácia Instituição/País de afiliação: Children's Hospital "Srebrnjak"/HR / GlaxoSmithKline Research Centre Zagreb Ltd/HR / Institute for Medical Research and Occupational Health/HR / Ru&#273;er Boskovi&#263; Institute/HR / University Hospital Zagreb/HR / University of Zagreb/HR