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Pharmacogenomics J ; 8(1): 16-22, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17440430

RESUMO

We examined whether survival of different rat strains administered anthrax lethal toxin is genetically determined. A reproducible test population of first filial generation hybrid rats was bred based on the susceptibility of progenitors to anthrax lethal toxin and to maximize genetic diversity across the strains. These rats were then tested with varying doses of anthrax lethal toxin. We found that all 'sensitive' strains died within 2 h following systemic administration of 240 mug/kg lethal toxin, while one strain survived following a five times higher dose (1.4 mg/kg). The ability of lethal toxin to lyse macrophage cultures derived from the bone marrow of these strains corresponded with in vivo results. We conclude that a rat test population can detect strain differences in response to anthrax lethal toxin. Survival is influenced by the host genome background and is likely due to a single gene with a recessive mode of inheritance.


Assuntos
Antígenos de Bactérias/toxicidade , Toxinas Bacterianas/toxicidade , Animais , Cruzamento , Separação Celular , Células Cultivadas , Resistência a Medicamentos , Genoma , Macrófagos/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Ratos Endogâmicos WKY , Especificidade da Espécie , Análise de Sobrevida
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