Exposure of Mice to 1,2-Dichloropropane Induces CYP450-Dependent Proliferation and Apoptosis of Cholangiocytes.
Toxicol Sci
; 162(2): 559-569, 2018 04 01.
Article
en En
| MEDLINE
| ID: mdl-29228347
ABSTRACT
1,2-Dichloropropane (1,2-DCP) has been used as a paint remover in the industry. The International Agency for Research on Cancer reclassified this compound recently to group 1 (carcinogenic to humans) based on epidemiological studies of cholangiocarcinoma among offset-color proof-printing workers exposed to 1,2-DCP in Japan. Two-year rodent carcinogenicity bioassays demonstrated that 1,2-DCP induced tumors in liver and lung, but not in bile duct. The present study was designed to assess the toxic effects of 1,2-DCP on proliferation and apoptosis in mice bile duct and the role of cytochrome P450 (CYP450) in any such effect. Male C57BL/6JJcl mice were cotreated or untreated with 1-aminobenzotriazole (1-ABT), a CYP450 inhibitor, and exposed to inhalation of 1,2-DCP at 0, 50, or 250 ppm alone, or at 0, 50, 250, or 1250 ppm 8 h/day for 4 weeks. Exposure to 1,2-DCP increased proliferation and apoptosis of cholangiocytes and induced severe hepatic damage, but had no effect on the lungs. Cotreatment with 1-ABT abrogated the effects of 1,2-DCP on proliferation and apoptosis of cholangiocytes. The results revealed that 1,2-DCP induces proliferation and apoptosis of cholangiocytes and that this effect is mediated through CYP450.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Propano
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Conductos Biliares
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Carcinógenos Ambientales
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Apoptosis
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Sistema Enzimático del Citocromo P-450
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Proliferación Celular
Límite:
Animals
Idioma:
En
Revista:
Toxicol Sci
Asunto de la revista:
TOXICOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón