Styrene monomer primarily induces CYP2B1 mRNA in rat liver.

To determine the cytochrome P450 (CYP) primarily expressed after styrene exposure, seven forms of hepatic CYP mRNA in rats treated with 600 mg kg(-1) styrene were examined. CYP1A2, CYP2B1/2, CYP2E1 and CYP3A2 mRNA were observed using real-time LightCycler PCR. The amount of CYP2B1 mRNA was significantly increased, 47-fold compared with controls, suggesting that this CYP is the primary cytochrome P450 in rats exposed to styrene. Significant increases in the amount of CYP2E1, CYP1A2 and CYP2B2 mRNA were also observed after styrene exposure, and their increase levels were 3.1-, 1.7- and 1.7-fold higher than controls, respectively. Western blot analysis also indicated that the protein levels of CYP2B1, CYP2B2, CYP2E1 and CYP1A2 showed clear increases after styrene treatment, corresponding to their mRNA expression. CYP2C11 mRNA decreased significantly in rats after styrene exposure. CYP1A1 was detected at the mRNA level in rat liver, but it was not detected at the protein level. The expression of epoxide hydrolase (EH), involved in Phase I drug metabolism, was also examined. EH mRNA increased 2-fold compared with controls after styrene exposure. Styrene thus appears to be a chemical compound that induces multiple CYPs. The results demonstrate that CYP2B1 is the primarily induced CYP form by styrene treatment to rats at acute toxic level.

The effect of silver administration on the biosynthesis and the molecular properties of rat ceruloplasmin.

To examine the cause of the altered ceruloplasmin (Cp) metabolism by silver administration, we analysed the properties of serum Cp by gel filtration chromatography, affinity chromatography and polyacrylamide gel electrophoresis. Metal contents in the Cp fraction from the silver-treated group were estimated as approximately 0.8 atom of silver and 4.2 atoms of copper per molecule, and as 5.9 atoms of copper for the control group. These findings confirm that holo-Cp from rat serum administered with silver nitrate exists as a silver-bound inactive form, suggesting that silver displaces one of Cp's copper atoms associating with oxidase activity. Matured holo-Cp also appeared in the Golgi in both groups, however, the amounts of enzymatically active holo-Cp showed a decrease after silver administration, while the apo-Cp level was hardly changed. These findings suggest that silver-bound holo-Cp is accomplished at Golgi.

Organ distribution of silver and the effect of silver on copper status in rats.

Tissue distribution of silver, alteration in tissue concentration of copper, zinc and iron, as well as changes in serum ceruloplasmin (CP) status were investigated in Fischer 344 rats after intraperitoneal (i.p.) administration of silver (9.3 mumol Ag/kg body wt.) as silver nitrate alone or combined with zinc (46.5 mumol Zn/kg) as zinc sulfate once a day for six successive days. Silver deposited in all the tissues examined, particularly in the pancreas, showing silver concentration in the serum, kidney, heart and lung to be significantly increased by simultaneous injection of zinc, while zinc concentration in the liver, pancreas and heart was significantly affected by silver. The most prominent effect of silver administration was observed in the copper status. As the result of altered copper metabolism by silver administration, copper concentration in the liver, pancreas and kidney was significantly changed, and serum copper concentration and CP oxidase activity were decreased to 60% and 25% of the control value, respectively. However, immunoblot analysis of serum CP in silver-treated groups showed only a slight decrease in protein levels, suggesting that most of the CP existed as an oxidase inactive apo-form. Simultaneously administered zinc hardly affected such changes. These results indicate that silver administration causes a disturbance of copper metabolism, and that zinc hardly plays a protective role against such changes.

Accumulation and declination of chlordane congeners in mice.

A metabolic experiment involving technical chlordane in mice was carried out in vivo by single and repeated oral administration. In the single oral dose group, residues of trans- and cis-chlordane in mouse whole body showed a maximum content at 5 hours after administration; thereafter, the body content decreased rapidly. For other congeners, the residues of trans- and cis-nonachlor reached a maximum at 10 hours, the residual levels forming a plateau. The intermediate metabolite oxychlordane was detected 1 hour after the administration of technical chlordane, the content in the mouse body increasing with time. In the repeated oral dose group, although technical chlordane was administered repeatedly, increases in trans- and cis-chlordane content were not observed for 29 days. On the other hand, the nonachlor and oxychlordane content increased gradually throughout the observation period. These findings suggest that the accumulation of nonachlors and oxychlordane in the animal body must be high and sufficient attention must be paid to their toxic effect.

Distribution and accumulation of [2,3-14C]acrylonitrile in rat after single injection.

The distribution and accumulation of acrylonitrile after the single i.p. injection of [2,3-14C]acrylonitrile were examined by whole-body autoradiography and by the determination of 14C radioactivities in several tissues and subcellular fractions after a whole-body perfusion. 14C Radioactivity was seen strongly in blood, particularly in red blood cells, and in several tissues including lung, liver, and kidney. Longer retention of radioactivity in brain and muscle was observed. At the subcellular level a relatively high specific radioactivity was seen in cytosol fractions of the brain, liver, and kidney.