Animal model for age- and sex-related genotoxicity of diethylstilbestrol
Braz. j. med. biol. res
;
42(11): 1090-1096, Nov. 2009. ilus, tab
Article
Dans Anglais
| 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.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Réticulocytes
/
Cancérogènes
/
Modèles animaux
/
Diéthylstilbestrol
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
langue:
Anglais
Texte intégral:
Braz. j. med. biol. res
Thème du journal:
Biologie
/
Médicament
Année:
2009
Type:
Article
Pays d'affiliation:
Croatie
Institution/Pays d'affiliation:
Children's Hospital "Srebrnjak"/HR
/
GlaxoSmithKline Research Centre Zagreb Ltd/HR
/
Institute for Medical Research and Occupational Health/HR
/
Ruđer Bosković Institute/HR
/
University Hospital Zagreb/HR
/
University of Zagreb/HR
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