We investigated the tissue-specific effects of dichlorodyphenyltrichloroethane (DDT) isomers in adult and suckling newborn mice, using a novel mouse line engineered to express a reporter of estrogen receptor transcriptional activity (ERE-tkLUC mouse). The DDT isomers p,p'-DDT [1,1,1-trichloro2,2-bis(p-chlorophenyl) ethane] and o,p'-DDT [1,1,1-trichloro-2(p-chlorophenyl)-2-(o-chlorophenyl) ethane] were specifically selected as a weak and a strong estrogen, respectively. In adult male mice, p,p'-DDT induced luciferase activity in liver, brain, thymus, and prostate but not in heart and lung. The effect of p,p'-DDT was dose-dependent, maximal at 16 h after sc treatment, and completely blocked by the estrogen receptor antagonist ICI-182,780. In all the organs analyzed, except the liver, administration of o,p'-DDT showed a pattern of luciferase induction superimposable to that of its isomer p,p'-DDT. In liver, o,p'-DDT significantly decreased basal luciferase activity and blocked the reporter induction by 17beta-estradiol. These data lead us to hypothesize that a modulation of ER activity may be involved in the toxic effects of DDT demonstrated by epidemiological and experimental studies. Luciferase activity was also studied in 4-d-old mice lactating from a mother injected with either p,p'-DDT or o,p'-DDT. Both isomers induced a 2-fold increase in the newborn brain. An opposite effect was observed in liver, where p,p'-DDT increased and o,p'-DDT decreased luciferase, thus indicating that these compounds modulate ER activity in adult and newborn tissues by use of a similar mechanism. The ERE-tkLUC mouse proves to be a suitable tool to functionally assess the tissue specificity of estrogenic/antiestrogenic compounds in adult (as well as in suckling) mice.
Isomer-specific activity of dichlorodyphenyltrichloroethane with estrogen receptor in adult and suckling estrogen reporter mice / D. Di Lorenzo, R. Villa, G. Biasiotto, S. Belloli, G. Ruggeri, A. Albertini, P. Apostoli, M. Raviscioni, P. Ciana, A. Maggi. - In: ENDOCRINOLOGY. - ISSN 0013-7227. - 143:12(2002 Dec), pp. 4544-4551.
|Titolo:||Isomer-specific activity of dichlorodyphenyltrichloroethane with estrogen receptor in adult and suckling estrogen reporter mice|
CIANA, PAOLO (Penultimo)
MAGGI, ADRIANA CATERINA (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore BIO/18 - Genetica
|Data di pubblicazione:||dic-2002|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1210/en.2002-220448|
|Appare nelle tipologie:||01 - Articolo su periodico|