Phenobarbital mechanistic data and risk assessment: enzyme induction, enhanced cell proliferation, and tumor promotion.
Pharmacol Ther
; 71(1-2): 153-91, 1996.
Article
en En
| MEDLINE
| ID: mdl-8910954
ABSTRACT
Chronic exposure to high doses of phenobarbital (PB) causes hepatocellular adenomas in both mice and rats and hepatocellular carcinomas in some strains of mice. Long-term PB therapy has not been found to cause human tumors. PB is not DNA reactive, and most genotoxicity tests have yielded negative results. PB has been extensively studied as an epigenetic, rodent liver tumor promoter. At exposures causing rodent liver tumors, PB has measurable effects on hepatocytes PB inhibits cell-to-cell communication; PB induces enzymes, including P450 cytochromes; PB stimulates proliferation and inhibits apoptosis of hepatocytes in neoplastic foci. Threshold exposures for some of these endpoints coincide with the threshold exposure for tumorigenesis.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenobarbital
/
Carcinógenos
/
Neoplasias
Tipo de estudio:
Etiology_studies
/
Guideline
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Pharmacol Ther
Año:
1996
Tipo del documento:
Article
País de afiliación:
Estados Unidos