Recovery of hyperplastic responsiveness in rat liver after dosing with the peroxisome proliferator methylclofenapate.
Carcinogenesis
; 12(11): 2127-33, 1991 Nov.
Article
em En
| MEDLINE
| ID: mdl-1934299
ABSTRACT
Methylclofenapate (MCP) was administered daily by gavage (25 mg/kg) for 7 days to groups of adult male rats. Dosing was interrupted for 28, 35, 56, 70 or 84 days and then resumed (25 mg/kg by gavage at 0 and 24 h). During the second period of dosing animals were killed in groups of three at 6, 12, 18, 24, 30, 36, 42 and 48 h after the resumption of dosing. Hepatocytes in S-phase, labelled with bromodeoxy-uridine, were analysed by flow cytometry, cell sorting and microscopy. It was observed that total S-phase activity was just significantly elevated (approximately 20% of maximum) over corn oil controls after an interval of 28 days between initial and subsequent dosing periods. After an interval of 35 days total S-phase activity was approximately 65% of maximum, and full hyperplastic responsiveness, equal to that observed in naive animals given MCP, was detected after interruptions in dosing of 56, 70 and 84 days. The recovery of S-phase responsiveness during the interruptions in dosing was accompanied by an increase in the proportion of 2 X 2N hepatocytes from approximately 10% in animals dosed continuously with MCP, to approximately 11.4% after 28 days interruption, 17% after 35 days and control levels (approximately 20%) after 56, 70 and 84 days. Irrespective of the magnitude of the hyperplasia elicited by the second period of dosing with MCP, the proportion of 2 X 2N cells was reduced to the same levels as those observed in animals dosed continuously with MCP (approximately 10%). Very low S-phase activity (0.05%) was observed in animals dosed continuously with MCP, this level of activity being similar to that in animals given corn oil continuously.
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01-internacional
Base de dados:
MEDLINE
Assunto principal:
Clofenapato
/
Fígado
Limite:
Animals
Idioma:
En
Revista:
Carcinogenesis
Ano de publicação:
1991
Tipo de documento:
Article