A typical lot of Kanemi rice oil injested by patients with Yusho (PCB poisoning) and the blood, liver and adipose tissue of the patients were analyzed for individual congeners of polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) by gas chromatography and gas chromatography-mass spectrometry. The individual congeners identified were assayed for biological properties such as accumulation ability in the liver of monkeys and rats, inducing activities of benzo[a]pyrene 3-hydroxylase, benzphetamine demethylase and DT diaphorase in rats, and gravimetric changes of the thymus and liver in rats. Among the seven PCB congeners detected in Yusho patients, 2, 3, 4, 5, 3', 4'-hexa-CB seems to be the most related compound to Yusho by its strong effects on induction of the liver enzymes, and on atrophy of the thymus and hypertrophy of the liver in rats. PCDF congeners identified in the patients showed severe toxicity in rats than this PCB, exhibiting stronger enzyme induction and gravimetric changes of the tissues even at very low doses of 1-10 μg/kg. These PCDFs, especially 2, 3, 4, 7, 8-penta-CDF, were also very accumulative in the liver. Therefore, they are considered as the most important etiologic agents for current symptoms of Yusho.
Investigations were performed to explore changes in fetal toxicity induced by acetylsalicylic acid (ASA) in pregnant animals treated by various means for maternal alterations. The fetotoxicity induced by ASA (500mg/kg s.c.) was higher in rats than in mice. In mice with low enzyme activity, those displaying a longer sleeping time in pentobarbital-induced sleep, the ASA-fetotoxicity was higher than that of mice with shorter sleeping time. In rats pretreated with phenobarbital (0.05%), Zn (10 mg/l) and Cu (10 mg/l) in tap water and cysteine (200 mg/kg s.c.), fetal toxicity of ASA was reduced, whereas it was enhanced in rats pretreated with SKF-525A (20 mg/kg s.c.) and a-naphthyl acetic acid (200 mg/kg p.o.) and in nephrectomized rats. The UDPGT activity in hepatic 9000×g supernate was higher in mice than in rats and the activity of mice was increased by phenobarbital and Cu. This study indicates that ASA-induced fetotoxicity can be positively modified by alterations in drug metabolizing activity.
The Lineweaver-Burk plot of the activity of human serum cholinesterase against the concentration of butyrylthiocholineiodide was shown by two intersecting lines. The Hill plot of cholinesterase activity was linear over the entire range of the substrate concentration. The n value, an interaction coefficient, was less than 1.0 (about 0.8). These results suggest that cholinesterase has multiple substrate binding sites. Acephate, one of the organophosphorous insecticides, inhibited the activity of cholinesterase. Acephate at concentration under 1.25 mM (about 230 ppm in serum) did not inhibit the activity of cholinesterase. The minimum concentration of acephate inhibition of cholinesterase activity was at 2.5 mM. An equillibrium constant (K') can be used as an indicator of inhibitory effect on cholin esterase. The serum cholinesterase activity of workers who were exposed to acephate is not affected when the concentration of acephate in serum is less than 200ppm. This result suggests that the activity of serum cholinesterase is not an accurate indicator of the exposure of the low toxic insecticides, e.g. acephate. The inhibitory effect of acephate on cholinesterase decreased after the incubation with S-9 mixture. This result suggests that a part of acephate is metabolized to inactive substances in the liver.
Forty-four kinds of organic nitrogen compounds as well as 37 kinds of dyes which contained nitrogen were subjected to TLm test by use of Himedaka (Oryzias latipes), and the results were compared with their partition coefficients between n-octanol and water. Concerning organic nitrogen compounds, such good correlation was observed among them that the larger the partition coefficient was, the smaller was the TLm value. Their acute toxicity to fish was supposed to be revealed after their passage through cell membrane of fish to be accumulated in the body. As far as coal-tar dyes and dyestuffs were concerned, there was a correlation between partition coefficient and TLm value. Methylene blue and rose bengale showed strong acute toxicity to fish and it was assumed that high affinity of these dyes to gill was responsible to depressing the function of gill, to make fish suffer from anoxemia and die.
Knowledges on the characteristics in toxicity of methylmercuric chloride (MMC), obtained in the present series of experiments in vitro, would be summarized as follows: (1) No appreciable cell-phase-specific age-response to MMC through the cell cycle of JTC-11 line of cells in vitro was shown. Cytolethal sensitivity of the mitotic cells to MMC was equal to that of the exponentially growing cells. (2) Culture media were prepared in graded concentrations of serum proteins and the various albumin/globulin ratios. Cytolethal toxicity of MMC in the graded treatment periods and concentrations was assayed in the prepared media. The apparent MMC toxicity was decreased both by albumin and by globulin. The both serum proteins appeared to be cytoprotective from MMC toxicity. In culture medium containing albumin, or inactivated bovine whole serum, the cytolethal toxicity of MMC was not observed in the MMC treatment concentrations below 0.5 μg/ml, but it was observed for any MMC treatment periods in the any concentrations above 0.5 μg/ml. Increases in the concentrations of either albumin or globulin, or the both, correlated with the decrease of MMC toxicity. (3) MMC uptake to the given number of cells was measured and decreased MMC uptake of cells in the medium containing serum protein, compared with that in the serum-protein-free medium, was obtained. Rapid transfer of MMC from the cells to the MMC free medium was observed during the first 30 min after the MMC treatment, which was followed by a slower exponential regression of MMC content of the cells during the successive incubation in the MMC free growth medium.
The localization of sudanophil material at dentine, the compact bone and epiphyseal cartilage plate of tibia of rat given beryllium carbonate was examined. Sudanophil material was seen at the boundary parts between dentine and widened predentine, and between widened preosseous matrix and calcified bone, but it was not seen at the area corresponding to the zone of provisional calcification. These facts suggest that the localization of sudanophil material in hard tissue of rat with Be rickets was similar to that in vitamin D deficient-induced rickets. This sudanophil material was not disappeared by the enzymes such as papain, pepsin and hyaluronidase as described in vitamin D deficient-induced rickets (Irving, 1960, 1963). Accordingly, it was suggested that the substance was not proteins and mucopolysaccharide.
At the onset of pentylenetetrazole induced convulsions, the adenylate cyclase activity and phosphodiesterase activity were increased. The former was markedly stimulated in the brain stem of rats. In the cerebral cortex and brain stem, the glucose level was significantly decreased, and the concentration of Alucose-6-phosphate was increased. However, the definite changes in energy reserve system of the brain could not be observed at the onset of penetylentetrazole induced seizures. The present study revealed some correlation between pentylenetetrazole convulsions and the adenylate cyclase activity and glycometabolism.