RESUMO
Se describen los efectos diferidos de la exposición prenatal a algunos compuestos orgánicos persistentes, por el mecanismo del imprinting (reprogramación celular). Entre estos compuestos están algunas dioxinas, policlorobifenilos, el DDT y su metabolico DDE, el metoxiclor, clordecona (kepone), dieldrina, lindano, benzo(a)pireno y pentaclorofenol. El mecanismo involucra alteraciones irreversibles en la diferenciación o en la programación de diversos tipos celulares, con cambios en las características de algunos de sus receptores hormonales, los que favorecen el desarrollo de diversas patologías más tarde en la vida. Entre los efectos que se detectan durante la edad adulta en animales o humanos expuestos perinatalmente, se destacan alteraciones neuroconductuales, retraso en el desarrollo cognitivo, depresión inmune, infertilidad y otras alteraciones del aparato reproductor masculino y femenino, cambios en concentraciones de receptores para diversas hormonas y neurotransmisores y cambios en la capacidad del hígado a inducir diversos sistemas enzimáticos.
Assuntos
Humanos , Feminino , Gravidez , Exposição Ambiental/efeitos adversos , Compostos Orgânicos , Efeitos Tardios da Exposição Pré-Natal , Clordecona , Poluentes Conservativos , DDT , Dieldrin , Dioxinas , Hidrocarbonetos Policíclicos Aromáticos , Hexaclorocicloexano , Pentaclorofenol , Bifenilos PolicloradosRESUMO
Why is a low dose of toxic chemical nontoxic? What makes a larger dose of the same chemical toxic? Extensive work done to understand the mechanism of halomethane hepatotoxicity and its potentiation by chlorinated insecticide, chlordecone has resulted in the understanding of these basic tenets of toxicology. Studies suggest that ordinarily a small dose of halomethane causes limited liver injury which is accompanied by stimulated tissue repair enabling complete recovery from injury before manifestation. A large dose of halomethane becomes toxic due to suppressed tissue repair, which permits injury to progress in an unchecked fashion. Exposure to very low levels of chlordecone results in highly exaggerated toxicity of ordinarily nontoxic doses of halomethane because of suppressed hepatocellular regeneration and restoration, permitting the progression of liver injury ultimately resulting in liver failure and animal mortality. This concept is further supported by the observation that, while exposure to even high levels of phenobarbital and subsequent low nontoxic doses of halomethane results in greater level of initial liver injury, tissue repair is not completely suppressed; it is slightly postponed by 24 hr, but then much higher rate of tissue repair ensures and consequently enables the animals to completely recover from liver injury and survive. Thus, whether initiation of tissue repair processes occurs or not is the critical determinant in the ultimate manifestation of hepatotoxicity and its end result of either animal death or recovery and survival. Currently understood 'Mechanisms of toxicity' adequately explain only how toxic injury begins. These mechanisms do not permit us to predict the ultimate outcome of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)