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Biomedical subjects

M Enomoto

Publications and source records attributed to M Enomoto.

At least 163 records · Page 9Linked to original sources

Usefulness and rapidity of screening for the toxicity and carcinogenicity of chemicals in medaka, Oryzias latipes.

The toxicity and carcinogenicity of number of chemicals, for which there are toxicity and/or carcinogenicity data in mouse and rat, were tested in medaka, a small aquarium fish (Oryzias latipes). The water-soluble chemicals were dissolved in the water and the water-insoluble chemicals were incorporated into the diet. Observation for 24 wk revealed induction of liver cell carcinoma by 6 chemicals; aflatoxins B1 and G1, sterigmatocystin, ortho-aminoazotoluene, methylazoxymethanol acetate and N-nitrosodiethylamine. In medaka fed PCB or DDT only preneoplastic liver cell nodules were observed. No evident carcinogenicity was found in medaka treated with 2-fluorenylamine, 2-fluorenylacetamide, DL-ethionine, luteoskyrin, ochratoxin A, phenobarbital, 1-(2-tetrahydrofuryl)-5-fluorouracil, sodium benzoate, 2,3,4,5,6-penta-O-acetyl-D-gluconyl isothiocyanate, citrinin and fusarenon X, respectively, although toxic lesions or hyperplastic changes were demonstrated histologically. These results confirm the practical utility and rapidity of the use of medaka for screening carcinogenicity and toxicity of chemicals, since neoplastic or toxic morphological changes develop rapidly following administration of relatively small quantities of test materials.

Adenoma↗

Chronic toxicity and hepatocarcinogenicity of (+) rugulosin, an anthraquinoid mycotoxin from penicillium species: preliminary surveys in mice.

(+) Rugulosin (RUG) is bis-anthraquinoid pigment produced by fungi such as Penicillium rugulosum Thom, P. tardum and others, and its chemical structure is very close to (-) luteoskyrin, one of bis-anthraquinoid pigments of Penicillium islandicum Sopp and hepatocarcinogenic to mice and rats. This investigation was concerned with the subacute and chronic effects of RUG on hepatic injury and hepatocellular tumor induction in male mice fed purified diets for 22 days containing 1.5 mg/5 g diet/animal per day or whole feeding period containing 0.3 and 0.75 mg RUG/5 g diet/animal per day. A half of male DDD mice receiving 1.5 mg RUG for the initial 22 days of feeding died 1-3 weeks thereafter from the acute hepatic injury characterized by fatty degeneration and liver cell necrosis, and hepatocellular carcinoma developed in one out of 14 mice surviving the feeding of control diet for additional 400 days. Each one fourth of cases of male ddYS mice receiving 0.3 and 0.75 mg RUG for 500-700 days developed hyperplastic nodules of liver cells. These data suggest that RUG is possibly a weak hepatocarcinogen for male mice with a potency les than one tenth of (-) luteoskyrin.

Animals↗

Report of carcinogenesis bioassay of sodium benzoate in rats: absence of carcinogenicity of sodium benzoate in rats.

The carcinogenicity of sodium benzoate was examined in Fischer 344 rats. Sodium benzoate was administered in the diet for 18 to 24 months at two dose levels; concentrations of 2% and 1% in the diet, which corresponded to the maximum tolerated dose (MTD) and 1/2 MTD as estimated from the data obtained by 6-week toxicity study. Fifty males and 52 females each were used per group. Controls consisted of 25 male rats and 43 female rats. No adverse clinical signs directly attributable to the compound were observed in treated animals. Differences in the average body weight, and mortality rates between treated and control groups were negligible. The results of the statistical test for dose-related trends were not significant (p < 0.05) Although a variety of tumors occurred among test and control rats of each sex, tumors appearing in treated rats were similar in type and number to those in controls. It was concluded that no evidence of carcinogenicity in rats from sodium benzoate was demonstrated.

Animals↗

Temperature-sensitive Chlamydomonas mutants manifesting flagellar regression at a restrictive temperature.

The regeneration kinetics of Chlamydomonas reinhardtii mutants TS-6 and TS-79, whose flagella were mechanically amputated, indicated that the flagellar precursor in cytoplasm was used for regeneration when cycloheximide was present. The TS-6 cells rendered nonflagellate by regression at 35 C did not regenerate in the presence of cycloheximide, indicating that the precursor was inactivated by the high temperature. Neither mutant was able to use the absorbed flagellar components for regeneration in the presence of cycloheximide.

Animals↗

Development of myogenic sarcomas in mice at the site of injection of 4-HAQO -- a study on the morphogenesis of tumor.

The morphological changes induced by a carcinogenic agent have been studied by serial histological examinations on the injection-sites in subcutaneous tissue of mice. As a carcinogen, 4-hydroxy-aminoquinoline-1-oxide was freshly suspended before use in olive oil (0.1 mg/0.1 ml) and injected subcutaneously into the right thigh of mice sixteen times at seven days intervals. Tumors were induced immediately after the sixteenth injection. Based on light and electron microscopic findings, these tumors were considered to be rhabdomyosarcomas. Morphologically, the course of the tumor induction was summarized as follows. The stage of inflammation (1-4 weeks), the stage of necrosis (4-8 weeks), the stage of the appearance of atypical cells (8-15 weeks), and the stage of tumor development (16 weeks and thereafter).

4-Hydroxyaminoquinoline-1-oxide↗

Integration, at hag or elsewhere, of H2 (phase-2 flagellin) genes transduced from Salmonella to Escherichia coli.

A fla mutant of E. coli K12 was given fla+ and H1-i by phage P1kc cotransduction from S. typhimurium, then made Fla- by transduction of ah1 from S. typhimurium. Motile clones expressing a Salmonella phase-2 antigen, e,n,x or 1,2, were obtained from the K12 i ah1 (therefore Fla-) line by P1kc transduction of flagellin-specifying genes, H2-e,n,x or H2-1,2, from Salmonella donors. Of eighteen such transductants sixteen failed to show phase variation, and on transduction back to Salmonella each structural gene for a phase-2 flagellin (or at least for its antigenically determinant part) now behaved as an allele of H1, presumably in consequence of incorporation in the hag region of the K12 recipient, in place of H1-i ah1. The e,n,x- and 1,2-specifying genes were shown to have been integrated in the K12 chromosome without the linked H1-repressor gene or the adjacent vh2 gene (controlling rate of phase-variation) and they responded to the repressing activity of an H2 allele elsewhere in the cell, in this respect resembling H1 alleles of Salmonella or hag alleles of E. coli. Two K12 e,n,x transductants had flagellin-specifying genes which when transduced back to Salmonella were integrated at H2; they are inferred to have resulted from integration of H2-e,n,x in the K12 chromosome elsewhere than the hag region. These two clones showed phase variation, between a Fla+ phase, with antigen e,n,x, and a Fla- phase (with e,n,x determinant in the nonactive state and the determinant of antigen i inactivated by ah1). The two integrated e,n,x genes when in the "active" state retained the ability to repress expression of exogenote H1 alleles, which indicates that the closely linked H1-repressor gene also was integrated. One of the two exceptional transductants derived its e,n,x gene from a Salmonella donor with the linked vh2- gene, which in Salmonella almost entirely prevents change of phase, and transduction of this e,n,x gene back to Salmonella recipients proved that vh2- had been incorporated into the E. coli chromosome along with the e,n,x determinant and the H1-repressor gene. The high frequency of change of phase (Fla+ in equilibrium Fla-) in the K12 e,n,x vh2- transductant concerned suggests that vh2- fails to prevent frequent change of state of the phase-determined part of H2 when vh2- and H2 are incorporated in the E. coli chromosome.

Bacterial Proteins↗

Toxicological approaches to the toxic metabolites of Fusaria. VIII. Acute and subacute toxicities of T-2 toxin in cats.

Acute and subacute toxicities to cats of T-2 toxin, 12-13 epoxytrichothec mycotoxin from fungi Fusarium species and others, were investigated. Major symptoms of toxicity in cats as the result of T-2 toxin were emesis, vomiting, diarrhea, anorexia, ataxia of the hind legs, discharge from the eyes and ejection of hemorrhagic fluid. Consecutive administration of the crude and pure sample of T-2 toxin in a sublethal dose caused a marked decrease in the number of circulating white blood cells. In the early stage of intoxication, a temporal leukocytosis was observed after each administration. Autopsy revealed extensive cellular damages in the bone marrow, intestine, spleen and lymph nodes. Greatly evident were meningeal hemorrhage of the brain, bleeding in the lungs and vacuolic degeneration of the renal tubles. Mycotoxicological significance of T-2 toxin and related trichothecenes is discussed in relation to the food-borne diseases in humans and farm animals.

Animals↗