| Autor: |
Z, Mureşan, A, Stoica, N, Stafidov, N, Voiculetz |
| Rok vydání: |
1987 |
| Předmět: |
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| Zdroj: |
Neoplasma. 34(5) |
| ISSN: |
0028-2685 |
| Popis: |
By the use of the dextran-coated charcoal method the presence of a high-affinity binding site for benzo(a)pyrene in the cytosol from rat liver (R strain) has been demonstrated. This binder was saturable by ligand concentration and by time. Sucrose density gradient analysis after charcoal treatment revealed one major peak of radioactivity sedimenting at 4.4 S which was displaceable by a 100-fold molar excess of nonlabeled benzo(a)pyrene. Benzo(a)pyrene binding to liver cytosol was sensitive to protease treatment of the cytosol suggesting that the binder was a protein. Saturation and Scatchard plot analysis of benzo(a)pyrene binding indicated a high-affinity (Kd = 4.7 nmol) and a relatively low binding capacity (Bmax = 379 fmol/mg cytosolic protein), allowing, to denote this binder as a receptor for benzo(a)pyrene. Competition studies showed that this cytosolic receptor was distinct from steroid hormone receptors since benzo(a)pyrene binding was partially inhibited by aromatic carcinogens 3-methylcholanthrene and benz(a)anthracene but not by estradiol, progesterone or cortisol. R strain rats used in these experiments were sensitive to induction with 3-methylcholanthrene which produced the increase of cytochrome Pl-450 content in liver microsomes, enhanced the glutathione S-transferase activity in hepatic cytosol and produced liver hypertrophy in stimulated animals. All these effects were related to the dose of 3-methylcholanthrene used for the induction. Also, the cytosolic binding capacity for benzo(a)pyrene was increased in animals stimulated with 3-methylcholanthrene in a dose-dependent fashion. The 3-methylcholanthrene-induced binder displayed identical sedimentation velocity and kinetic parameters (Kd) to those characteristic for the benzo(a)pyrene receptor in hepatic cytosol from unstimulated animals. Conclusively, our results demonstrated that benzo(a)pyrene was bound to a receptor protein in rat liver cytosol which was inducible by the classical inducer 3-methylcholanthrene. The mechanism of induction of this receptor and its role in cell response to aromatic carcinogens still need to be elucidated. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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