[Tissue distribution, inductive effect on liver enzymes and acute toxicity of 2,3,4,7,8-pentachlorodibenzofuran in Golden Syrian hamsters].
The hamsters have been known to be the least sensitive mammalian species to the acute toxicity of highly toxic polyhalogenated hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. In the present study, the tissue distribution, inductive effect of liver enzymes and acute toxicity of 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) in male Golden Syrian hamsters were examined. The highest content (about 48% of dose) of PenCDF was found in the liver 5 days after a single i.p. dose of 1.0 mg/kg. The amount ranging about 5 to 10% of dose was also distributed to mesentery, skin and muscle. In liver, the distribution of PenCDF was just parallel to that of cytochrome P-450 (P-450), marker enzymes of liver endoplasmic reticulum, suggesting that PenCDF binds to P-450. The mode of inductive effects of PenCDF in hamsters was 3-methylcholanthrene-type as reported previously in rats. However, the typical enzymes such as benzo(a)pyrene 3-hydroxylase and DT-diaphorase were induced to a relatively less extent than did in rats. In hamsters pretreated with PenCDF at a dose of 0.5 mg/kg, the potent atrophy of thymus and the 3-fold increase of liver lipid peroxide were observed, whereas the body weight gain was not suppressed at all. These results suggest that the induction of liver enzymes and the atrophy of thymus might not be the direct cause of PenCDF-induced lethality in hamsters.
Koga
N
N
Nakashima
H
H
Kamimura
H
H
Hokama
Y
Y
Yoshimura
H
H
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001572:Benzofurans / Q000493:pharmacokinetics / Q000633:toxicity*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism*; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000201:enzymology*; D008297:Male; D008647:Mesocricetus; D014018:Tissue Distribution
D001572:Benzofurans; D003577:Cytochrome P-450 Enzyme System; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; C038890:2,3,4,7,8-pentachlorodibenzofuran