Mutagenicity of 6 aminobenzene derivatives against Salmonella typhimurium TA 98 was studied in the presence of various S9 fractions. S9, which has been prepared form the livers of rats, hamsters and mice after pretreatment with different types of inducers ; polychlorinated biphenyls, phenobarbital and 3-methylcholanthrene, was used as the methabolic activating enzyme in this mutation assay. The S9 fractions from 3-methylcholanthrene-treated rats and mice are most useful for mutation induction by the all aminobenzenes used. The mutagenic activity of the compounds was clearly correlated to 3-methylcholanthrene-induced cytochrome P-450. However, any significant correlation between aniline hydroxylase activity and the mutagenesis was not observed.
Analysis of the liberation degrees of intracellular materials from Ehrlich ascites tumor cells by treatment of Triton X-100 was performed. The liberation process has two stages. In the first stage, cytoplasmic inorganic phosphorus were liberated at a concentration of about 0.01% of the detergent, and in the second stage macromolecules such as lysosomal enzymes were liberated at a concentration of about 0.03% of the detergent. Morphologically, the cells began to swell in the first stage but were not stained by Trypan blue, and the cells in the second stage became fully swollen and ruptured. The staining curve of the swollen and ruptured cells was closely in parallel with the liberation curves of the macromolecules.
The metabolic detoxication of thymol was investigated in rabbit and man. Thymol glucuronide which the aglycone is intact, was isolated from thymol medicated rabbit urine and identified as a acetyl derivative of methyl glucuronate. The hydroxylated product of thymol, thymohydroquinone, was recognized in a small amount in thymol medicated human urine. It was presumed that thymohydroquinone is excreted as ethereal sulfuric acid conjugate in man.
The effects of methylmercury chloride and other mercury compounds on cholinergic parameters were studied in vitro. Methylmercury chloride (MMC) and phenylmercury acetate inhibited choline acetyltransferase (ChA)/th 20 μM of I<50>, and mercury nitrate (MN) with 100 μM of I<50>. All the three compounds had little effect on cholinesterase activity. MMC inhibited a high affinity choline uptake with 41μM of Ki, as well as a low affinity choline uptake with 250μM of Ki. MMC did not affect a spontaneous and potassium-stimulated ACh release from brain tissue slices incubated in eserinized Krebs-Ringer's solution up to the concentration of 100 μM. It was shown that the organic mercury compounds, such as methylmercury, were potent inhibitors of the choline uptake systems, as well as ChA activity.
Semiacute toxicity of cola fluid, Coca-Cola, conducting for approximately a month in rats, was studied. A trend of cariogenicity of Coca-Cola was strongly indicated. When the fluid was given ad libitum, decarbonized Coca-Cola and carbohydrate solution, consisted 8% of glucose and 3.5% of sugar and then adjusted pH to 2.4 with oxalic acid, were consumed 2 to 3 times greater than the control (water). A hyperuredis was observed as the result of great consumption of liquid, but no liver nor kidney degeneration was observed by histopathological examination. The diet consumption of the groups of Coca-Cola and carbohydrate solution was approximately a half of the control, water. However, when a complete diet was given, no physiological difference in time was observed, except in diarrhea and depression of hair gloss in Coca-Cola group.
Plasma aspartate levels were measured after potassium aspartate administration through different routes to rats of various ages. The changes in plasma levels were most significant with intraperitoneal injection. Dose- and age-related responses to aspartate load were obtained. The present data suggest that a marked elevation of plasma aspartate levels may result in neuronal necrosis. By comparing the plasma aspartate levels with the results on hypothalamic lesion (Okaniwa et al., 1979), plasma peak value associaed with the lesion was estimated in each case of various administration routes and rat ages.
Cellular and humoral immunological phenomena in rabbits treated with tetracycline were investigated by lymphocyte transformation, leucocyte migration inhibition, and indirect hemagglutination tests. Cellular and/or humoral immunity against tetracycline and/or homologous or autologous rabbit gamma globulin was acquired by about two-thirds of the rabbits, with some also acquiring immunity against homologous tissue antigen after prolonged tetracycline administration. Based on these results, the significance of immune responses to autoantigens by drug administration was discussed in relation to potential agents for the induction of autoimmune diseases.
To clarify the light and electron microscopic changes accompanying embryonic death from a lethal dose of arsenic acid, MP 1 pregnant rats were injected i.p. with 30 mg/kg arsenic acid at 1:30 p.m. on day 9 of gestation (the neurulation stage). At 4 hours after treatment, some cell necrosis occurred in the neuroectoderm and the mesoderm of the embryo. At six hours later, cell necrosis increased in the neuroectoderm and the mesoderm, whereas those in the surface ectoderm and the endoderm were very few. In the embryo 12 hours after treatment: abnormal mitotic cells exhibiting vesiculation of the endoplasmic reticula, and abnormal interphase cells characterized by the ring-shaped nucleoli in the nucleus and the enlargement of cisternae of the endoplasmic reticula and the nuclear envelope, were observed in the neuroectoderm and the mesoderm. Debris from cell necrosis and the said abnormal mitotic and interphase cells were ejected from the neuroectoderm into the amniotic coele. In the embryo 24 hours later: neurulation was stopped and the V-shaped neural fold remained. The somite formation was retarded. The surviving cells in the embryo sometimes contained phagocytic vesicles in the cytoplasm, but no other anomalies were encountered. It was considered that a variety of metabolic reactions may be disturbed by arsenic acid, resulting in numerous cell necrosis and abnormal mitotic and interphase cells in the neuroectoderm and the mesoderm of the rat embryo.
The strong complex formations of pyridine nucleotides with mercury compounds were demonstrated in artificial intracellular fluid containing oxianions (HPO4<2->, HCO3-), while those in artificial extracellular fluid were considerably weaker. Dissociation constants (K) of the complexes of [MC·NADP], [MC·NADPH], [MC·NAD], [MC·NADH], [MC·adenine], and [MC·nicotinamide mononucleotide] were found to be 1.0×10<-4>, 2.6×10<-5>, 1.2×10<-4>, 2.9×10<-5>, 7.2×10<-6>, and 3.8×10<-8>, respectively in phosphate buffer (43 mM, PH 8.0).