| Autor: |
R, Kimura, M, Kawai, Y, Kato, M, Sato, T, Aimoto, T, Murata |
| Rok vydání: |
1985 |
| Předmět: |
|
| Zdroj: |
Toxicology and Applied Pharmacology. 78:300-309 |
| ISSN: |
0041-008X |
| Popis: |
The increases in the hepatic microsomal aminopyrine N-demethylase activity and in the content of cytochrome P-450 produced by m-dichlorobenzene (m-DCB) occurred after increases in the hepatic concentration of 3,5-dichlorophenyl methyl sulfone, a minor metabolite. The extent of increases in aminopyrine N-demethylase activity and in the content of cytochrome P-450 at 48 hr after po administration of 200 mg/kg (1.36 mmol/kg) of m-DCB was almost equal to that 72 hr after the ip administration of 25 mumol/kg of the sulfone (Kimura et al., 1983). m-DCB in liver was not detectable at that time, and the concentration of sulfone was 63 to 70% of that 48 to 72 hr after the ip administration of 50 mumol/kg of sulfone. Administration of m-DCB (200 mg/kg) produced a significant reduction in hexobarbital sleeping time, but this reduction was less than that produced by administration of the sulfone (50 mumol/kg). The protein band patterns by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the microsomes from rats treated with the sulfone and m-DCB were similar to those of phenobarbital-treated rats but were different from those of 3-methylcholanthrene-treated rats. The sulfone showed type I interaction with the cytochrome P-450 (Ks, 0.17 mM). The sulfone was formed from the sulfide but reduction of the sulfone was not observed when it was incubated in a hepatic microsomal preparation. The pattern of induction by the sulfone and m-DCB was similar to that by phenobarbital and differed from that by 3-methylcholanthrene. From these results, 3,5-dichlorophenyl methyl sulfone is considered to be a major contributing factor of the inducing activity of m-DCB and to be a potent phenobarbital-like inducer. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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