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1.
Environ Res ; 61(1): 157-63, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8472670

RESUMO

Toxic chemicals in the environment can cause a wide range of neurological disease. High-dose exposures to environmental neurotoxicants have produced encephalopathy in children ingesting chips of lead-based paint, blindness in persons who ingested methanol, blindness and ataxia in persons who consumed organic mercury, spinal cord degeneration and peripheral neuropathy in persons exposed to tri-ortho-cresyl phosphate (TOCP), and Parkinsonism in persons exposed to MPTP or to manganese. Environmental neurotoxicants have also been shown to produce a wide range of subclinical neurotoxic effects, including reduction in intelligence, impairment in reasoning ability, shortening of attention span, and alternation of behavior. The first step in the prevention of environmental neurotoxicity is to test chemicals for their toxic potential. More than 70,000 chemicals are currently in commerce. However, except for pharmaceuticals, fewer than 10% of these chemicals have been tested for neurotoxicity. A logical approach to neurotoxicologic assessment of chemical substances will build on and extend currently available test systems. It will have a tiered structure. The first or screening tier will consist of tests to measure obvious structural and functional changes, often a functional observational battery. Subsequent levels of testing will be guided by the results of initial screening. Toxicologic testing must be supplemented by epidemiologic surveillance of populations exposed to known and suspect neurotoxicants. Screening programs in these populations designed to detect excessive absorption of a neurotoxic agent or subclinical neurological dysfunction can be useful in identifying affected individuals before severe disability occurs.


Assuntos
Poluentes Ambientais/toxicidade , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/prevenção & controle , Biomarcadores , Humanos , Toxicologia/métodos
2.
Toxicol Appl Pharmacol ; 87(2): 374-9, 1987 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3824391

RESUMO

The molecular pathogenesis of n-hexane neurotoxicity has been postulated to proceed as follows: The gamma-diketone metabolite, 2,5-hexanedione (HD), reacts with lysyl-amino groups on neurofilaments to form imines. The imines cyclize to form pyrroles. The pyrroles autoxidize, resulting in covalent protein-protein crosslinking within or between neurofilaments. A resultant impairment of neurofilament transport is proposed to lead to neurofilament-filled axonal swellings. This experiment was designed to test whether oxidation is a necessary pathogenetic step in vivo by comparing time of onset of paralysis of an HD treated group of rats to that of a group receiving HD plus oxygen under high pressure (OHP). The group of rats receiving the hyperbaric oxygen treatment reached the endpoint of hindlimb paralysis significantly sooner than the group receiving none. The fact that OHP does accelerate HD neuropathy points towards an oxidative step in the molecular pathogenesis of gamma-diketone neuropathy.


Assuntos
Hexanonas/toxicidade , Oxigenoterapia Hiperbárica , Cetonas/toxicidade , Sistema Nervoso/efeitos dos fármacos , Animais , Axônios/efeitos dos fármacos , Axônios/ultraestrutura , Peso Corporal/efeitos dos fármacos , Sinergismo Farmacológico , Filamentos Intermediários/efeitos dos fármacos , Filamentos Intermediários/ultraestrutura , Masculino , Paralisia/induzido quimicamente , Ratos , Ratos Endogâmicos
3.
Cancer Res ; 37(2): 436-9, 1977 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-832267

RESUMO

The 490 quinone, a natural sulfhydryl-arylating reagent from the mushroom, Agaricus bisporus, markedly inhibited L1210 murine leukemia DNA polymerase alpha while resulting in little inhibition of DNA polymerase beta from this source. This quinone was more strongly inhibitory than p-chloromercuri-benzoate or N-ethylmaleimide and was less readily neutralized by sulfhydryl-containing molecules such as dithioerythritol. Preliminary experiments indicate that DNA protects DNA polymerase alpha from inhibition by the 490 quinone. The inhibition of DNA synthesis by quinone 490 may contribute significantly to the cytotoxicity of this compound and to the potential of gamma-L-glutaminyl-4-hydroxybenzene as an antitumor agent.


Assuntos
DNA Polimerase II/antagonistas & inibidores , DNA Polimerase I/antagonistas & inibidores , Leucemia L1210/tratamento farmacológico , Inibidores da Síntese de Ácido Nucleico , Reagentes de Sulfidrila/farmacologia , Animais , Antineoplásicos , Sítios de Ligação , Cloromercurobenzoatos/farmacologia , DNA Polimerase I/metabolismo , DNA Polimerase II/metabolismo , DNA de Neoplasias/biossíntese , Ditiotreitol/farmacologia , Avaliação Pré-Clínica de Medicamentos , Etilmaleimida/farmacologia , Leucemia L1210/enzimologia , Leucemia L1210/metabolismo , Camundongos , Camundongos Endogâmicos DBA , Reagentes de Sulfidrila/metabolismo , Reagentes de Sulfidrila/uso terapêutico
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