Ikuko Ueno

Carcinogenicity examination of quercetin and rutin in ACI rats

Carcinogenicity of quercetin and rutin were examined in inbred ACI strain rats. Rats were given a diet containing 1% or 5% quercetin or 5% rutin for 540 days, or 10% quercetin and 10% rutin for 850 days. Rats in control groups were fed a normal basal diet. Most tumors found in experimental groups were also found in the corresponding control groups. Furthermore, there was no significant difference between the incidence of tumors in the experimental or control groups (P greater than 0.05). Thus, quercetin and rutin tested were not shown to be carcinogenic to ACI rats.

Fusarenon-X, a toxic principle ofFusarium nivale — Culture filtrate

Fusarenon-X, ein toxisches Produkt aus dem Kulturfiltrat vonFusarium nivale wurde isoliert, näher charakterisiert und dessen Struktur ermittelt.

Inhibitory effects of condiments and herbal drugs on the growth and toxin production of toxigenic fungi.

The effects of thirteen kinds of powdered herbal drugs and seven kinds of commercial dry condiments on the growth and toxin production ofAspergillus parasiticus, A. flavus,A. ochraceus, andA. versicolor were observed by introducing these substances into culture media for mycotoxin production.Of the twenty samples tested, cinnamon bark completely inhibited the fungal growth, while the others only inhibited the toxin production.The inhibitors were easily extracted from the samples with solvents such as hot water, chloroform, or ethanol.The extracts from coptis, philodendron bark, mustard, green tea leaves, and zanthoxylum completely inhibited the aflatoxin production ofA. parasiticus, however, they had little or no inhibitory effect againstA. flavus.

Analysis of blood plasma proteins in patients with Alzheimer's disease by two-dimensional electrophoresis, sequence homology and immunodetection.

Blood plasma proteins of patients with Alzheimers disease (AD; senile dementia) and non‐AD‐type dementia were resolved by two‐dimensional electrophoresis and identified by migration position in the electrophoresis pattern, sequence homology, and immunodetection by using antibodies. For the control experiments, blood plasma proteins of a healthy young individual and non‐dementia patients were examined in a manner similar to that of the plasma samples of AD patients. In the plasma sample of the healthy young individual, more than 350 spots of silver‐stained proteins were observed and among these spots, 73 spots were identified. Blood plasma proteins of the AD and non‐AD‐type dementia patients were compared with those of the control and non‐dementia patients. In the blood plasma samples of five AD patients, three patients had apolipoprotein E4, and another patient showed apolipoprotein L and complement factor H. For the AD‐related proteins apolipoprotein E, tau‐1, and presenilin 2, proteins were examined by immunostaining with antibodies, in both AD and non‐AD patients. Among the three samples of non‐AD‐type dementia patients, one was distinguishable by amyloid A proteins, and the other by haptoglobin isoforms.

Carcinogenic activity of Farfugium japonicum and Senecio cannabifolius

The carcinogenicity of Farfugium japonicum and Senecio cannabifolius was studied in ACI rats. In Group I, rats were given a diet containing 20% Farfugium japonicum. Groups II, III, IV and V were given diets containing 8%, 4%, 1% and 0.2% Senecio cannabifolius until the end of the experiment, respectively. The experiment was terminated after 480 days, except for Group V which was terminated 560 days after the start of feeding. Hemangioendothelial sarcoma of the liver and liver cell adenoma were induced in Groups I, IV and V. All rats in Groups II and III died of hepatotoxicity within a short period.

Ozone Exposure Generates Free Radicals in the Blood Samples In Vitro. Detection by the ESR Spin-Trapping Technique

Generation of free radicals in the reaction of ozone with blood samples and related salt solutions was investigated in vitro by using ESR spin-trapping technique with DMPO. In the reactions of low levels of ozone, a carbon-centered radical was spin-trapped with DMPO, giving rise to the 6-line ESR signal in both whole blood and blood plasma. In the blood plasma, DMPO-spin adduct of hydroxyl radical (DMPO-OH) was detected together with the spin adduct of carbon-centered radical. The present spin-trapping study demonstrates that, when exposed to ozone, 0.9% NaCl solution in the presence of DMPO gives rise to the formation of DMPO-OH. The addition effects of ethanol, which is a .OH scavenger, into the NaCl solution reveal that DMPO-OH is produced by the reaction of DMPO with both .OH and unidentified oxidants originated from the reaction of Cl- and ozone. Based on these observations, we consider that .OH is generated similarly in the blood plasma exposed to ozone. The ESR study of DMPO-spin adducts in the ozone-exposed aqueous solution of NaOCl indicates that Cl- reacts with ozone to give ClO-. Presumably, further oxidation of ClO- by ozone leads to the formations of .OH and the unidentified oxidants.

Characterization of neutrophil b-type cytochrome in situ by electron paramagnetic resonance spectroscopy

Electron paramagnetic resonance spectroscopy at 4.2 K was successfully used to characterize neutrophil b‐type cytochrome in situ. The spectra or resting neutrophils taken under aerobic conditions gave a set of characteristic signals in a high magnetic field (g=2.85, 2.21 and 1.67) beside signals for myeloperoxidase and others. From the g values, shapes and the results of other experiments, these signals were attributed to those of cytochrome b 558. The results indicate that cytochrome b 558 in resting neutrophils is a hexa‐coordinated ferric hemoprotein in a low‐spin state. The obtained g??? and g??? values for the hemichrome were consistent with that of bis(imiduzole)‐coordinated hemoprotein.

Effect of retinoic acid and 12-O-tetradecanoyl phorbol-13-acetate on the binding of epidermal growth factor to its cellular receptors

Binding of 125I-labelled epidermal growth factor (EGF) to C3H/2K cells and the effect of a tumor promotor, 12-O-tetradecanoyl phorbol-13-acetate (TPA) and of a tumor promotor antagonist, retinoic acid, on the binding was studied. Scatchard plot analysis of the binding showed the presence of two types of binding sites with different affinity to EGF. Treatment of the cells with retinoic acid for 1 h resulted in elevation of the affinity of both sites without changing their number per cell. Prolonged exposure to retinoic acid abrogated this elevation of the affinity and caused cycloheximide-sensitive increase of the number of the binding sites of both types. TPA inhibited binding of EGF to the cells by abolishing the binding to the high affinity sites, whereas retinoic acid, in the presence of TPA, enhanced it by increasing the number of the low affinity sites.

Impairments of RNA synthesis in Ehrlich ascites tumour by luteoskyrin, a hepatotoxic pigment ofPenicillium islandicum sopp

La lutéoskyrine, pigment cartinogène synthétisé par lePenicillium islandicum Sopp, inhibe la synthèse du RNA nucléaire dans la cellule de la tumeur Ehrlich.

Absorption, distribution and excretion of luteoskyrin with special reference to the selective action on the liver

Pharmacokinetic experiments with 3H-luteoskyrin disclosed the following findings on absorption, distribution and excretion of the compound: (1) Luteoskyrin (luteo), when administered sc or po, rapidly concentrates in the liver, reaching maximum concentration about 1 day after administration. Although similar uptake curves are shown by other organs, the maximum luteo value for the liver is singularly high. The trend toward selective concentration in the liver explains the specific hepatotoxicity of luteo. (2) Most luteo administered iv quickly disappears from the blood, and a considerable amount enters the liver. The effective concentration in the liver for hepatotoxicity is low but within definite limits and is nearly the same after sc and po administration. (3) The luteo uptake varies with different organs and tissues, and the amount entering the liver shows a wide difference depending on the route of administration. This accounts for the differences seen between the iv LD50 and those values obtained after sc and po administration. (4) A slow uptake of luteo by the liver and a time lag for development of liver damage were observed; this accounts for the slow onset of toxicity of luteo. (5) Elimination of luteo gradually takes place through the liver, gastrointestinal tract and kidney, and the residual luteo is detectable in the blood, feces and urine for many days.