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Biomedical subjects

I Hirono

Publications and source records attributed to I Hirono.

At least 73 records · Page 4Linked to original sources

Low-level chemiluminescence from Drosophila melanogaster fed with chemical mutagens polycyclic aromatic hydrocarbon quinones and a carcinogenic bracken fern.

The spontaneous photon emission (chemiluminescence) from Drosophila melanogaster fed chemical mutagens, polycyclic aromatic hydrocarbon quinones, and a carcinogenic bracken fern was studied. The fly chemiluminescence was evidently enhanced by mutagen or carcinogen administration and was increased proportionally to the administered amount of tested compound. Strong chemiluminescence was observed especially at the larval stage. Living larvae emitted stronger chemiluminescence than their homogenate. The chemiluminescence from Drosophila melanogaster fed polycyclic aromatic hydrocarbon quinones showed a linear relation with the mutation frequency in the Drosophila wing spot test. The chemiluminescence from flies fed a bracken fern decreased by the addition of free radical scavengers and active oxygen quenchers. The phosphatidylcholine hydroperoxide concentration in the flies was increased proportionally with the chemiluminescence intensity. It seems that the free radical formation is stimulated as shown by the enhanced chemiluminescence in mutagen- or carcinogen-dosed flies, and as a result, lipid peroxide accumulation accompanies mutation in Drosophila melanogaster.

Animals↗

Nucleotide sequence and expression of an extracellular hemolysin gene of Aeromonas hydrophila.

The extracellular hemolysin (AHH1) gene of Aeromonas hydrophila ATCC7966 was cloned into Charomid9-28 in Escherichia coli DH1, and its complete nucleotide sequence determined. Escherichia coli carrying this gene expressed an extracellular heat-labile hemolysin for rabbit red blood cells. The minimum size of the coding region of the 2.6 kilobase-pair BamHI-SphI fragment was subcloned into pUC118 and pUC119, selecting for hemolytic activity. The nucleotide sequence of this region contained a single open reading frame of 1734 base pairs, corresponding to a protein of 577 amino acid residues (63,658 daltons). A consensus promoter sequence was present upstream of the AHH1 open reading frame. Maxicell analysis of [35S]methionine-labelled proteins in E. coli CSR603 carrying the AHH1 plasmid suggested that AHH1 gene codes for an approximately 60,000 dalton polypeptide. By colony DNA-DNA hybridization analysis, the AHH1 gene was detected in 43 of 62 hemolysin-producing strains of A. hydrophila (isolated from various sources and areas) and in all 43 hemolysin-producing strains of A. salmonicida (isolated from fish). Three hemolysin-negative strains of A. hydrophila did not react with the AHH1 probe, whereas three non-hemolytic A. salmonicida strains hybridized with the probe.

Aeromonas hydrophila↗

Gastric lesions in rats fed salted food materials commonly eaten by Japanese.

A high intake of salted food is thought to be related to the high incidence of stomach cancer in Japan. In the present study, female F344 rats were divided into four groups. They were fed a nutritionally deficient purified diet (Group 1) and standard purified diet (Group 3) for 113 weeks and the same diets supplemented with salted cuttlefish guts, broiled, salted, dried sardines, pickled radish, and soy sauce (Groups 2 and 4). The incidence of papillomas and ulcers of the forestomach was highest in Group 4, which was given the standard diet supplemented with the salty food materials (p less than 0.05). These results suggest the importance of salted food as a suspicious causal factor in human stomach cancer in Japan.

Animals↗

Comparison of the effects of bilobol and 12-O-tetradecanoylphorbol-13-acetate on skin, and test of tumor promoting potential of bilobol in CD-1 mice.

Bilobol, isolated from ginkgo fruit pulp, has been noted to be a strong skin irritant like 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor-promoter in the skin. A comparative investigation of morphological changes induced by bilobol and TPA induced in the skin of CD-1 mice, and an assessment of the skin tumor promoting potential of bilobol were therefore performed. In experiment I, mice received a single application of 2.5, 50 or 1000 micrograms of bilobol, or 0.1 or 2.5 micrograms of TPA on the right ear. The 50 or 1000 micrograms bilobol and 2.5 micrograms TPA doses caused ear redness, epidermal thickening and inflammatory infiltration. The dose of 2.5 micrograms of TPA, which is usually used as tumor promoter in skin carcinogenesis, was equivalent to 50 micrograms of bilobol in irritant effect. Thus, 50 micrograms of bilobol was used for the promotion testing (experiment II) in CD-1 mice initiated with 100 micrograms of 7, 12-dimethylbenz[a]anthracene (DMBA). Treatment with either 10 or 50 micrograms bilobol twice a week for 30 weeks did not result in any tumor development, thus suggesting that bilobol is not a complete promoter of skin carcinogenesis, despite generation of inflammation.

9,10-Dimethyl-1,2-benzanthracene↗

Experimental induction of uterine cancer in rats by N-ethyl-N'-nitro-N-nitrosoguanidine dissolved in polyethylene glycol.

In the present experiment we attempted to experimentally induce uterine cancer in rats by injecting into the uterine cavity N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) dissolved in polyethylene glycol (PEG). Fifty-nine female F-344 rats, 7-8 weeks old, were divided into three groups and each received in the left uterine cavity with laparotomy a single dose of ENNG dissolved in PEG according to the following schedule: Group 1 received 75 mg ENNG/kg body wt.; Group 2 had 20 mg ENNG/kg body wt.: and Group 3 was given only PEG. In Group 1 it was observed that adenocarcinoma and sarcoma were present in the uterine corpus while squamous cell carcinoma occurred in the uterine cervix. In Group 2, although tumors such as adenocarcinoma, adenoma and sarcoma were observed in the uterine corpus, no tumor was present in the uterine cervix. No tumor growth whatsoever was observed in Group 3. From the above results it is apparent that the present method is an efficient means for experimentally inducing uterine cancer and that the site of tumor generation varies according to the concentration of ENNG administered.

Animals↗

Enhancing effect of ethanol on aflatoxin B1-induced hepatocarcinogenesis in male ACI/N rats.

The modifying effect of ethanol (EtOH) on aflatoxin B1 (AFB1)-induced hepatocarcinogenesis was examined in male ACI/N rats by chronic treatment at the post-initiation phase. Rats received an ip injection of AFB1 (1.5 mg/kg) twice a week for 10 weeks (a total of 20 doses). Following a week of acclimation, they were given 10% EtOH as drinking water for 56 weeks. The effect of EtOH on the hepatocarcinogenesis was evaluated in terms of the incidence of altered hepatocellular foci and neoplasms at the end of the experiment. Exposure to AFB1 alone induced a substantial number of altered foci (6.98 iron-excluding foci/cm2) in rats. The number of altered liver cell foci in rats receiving AFB1 followed by EtOH was significantly increased (26.39 iron-excluding foci/cm2). In the rats given EtOH after AFB1, the total area and mean diameter of both iron-excluding foci and altered foci identified in hematoxylin and eosin-stained sections were significantly higher than in the rats exposed to AFB1 alone. The incidence of liver cell tumors of the group given AFB1 and EtOH (3/15, 20%) was higher than that of the group treated with AFB1 alone (0/14, 0%). Treatment with EtOH alone for 56 weeks did not induce either. These results indicate an enhancing effect of EtOH on AFB1-induced hepatocarcinogenesis when it is given in the promotion phase.

Aflatoxin B1↗

[Solvent power of new denture cleaner for denture calculus and the influence of this cleaner on the denture materials].

In order to chemically remove the calculus adhering to a denture, new denture cleaner was prepared on an experimental basis. The principal ingredient of this solution was a chilating agent which contained the phosphoric acid. This study consisted of the fundamental and the clinical examinations of this solution the purpose of which was to test the solvent power of this solution on the calculus and to evaluate its influence on the denture materials and its effectiveness in clinical practice. 1. the fundamental study 1) method (1) The test for the solvent power of this solution. The powder of tricalcium phosphate (T.C.P. powder: Wakohjunyaku Co.) was substituted for the calculus adhering to a denture. (1) The influence of the solution temperature on the solvent power. The T.C.P. powder was dissolved at 20 degrees C, 30 degrees C, 40 degrees C, 50 degrees C and 60 degrees C temperature in 10 g of the solution within 10 minutes and the amount of dissolved powder was weighted. The time was measured with a stop watch (Seiko Co.) until 0.5 g of T.C.P. powder had been dissolved in 10 g of the solution. (2) The effect of using it with an ultrasonic cleaner. The time to dissolve 0.1 g of T.C.P. powder in 10 g of this solution was compared with that of the 15% EDTA solution. The measurement was repeated 5 times and the arithmetic mean of the 5 sample values was calculated in order to show the experimental results. The room temperature was 19 +/- 2 degrees C, the humidity was 56 +/- 3%. (2) The influence of this solution on the denture materials. (1) resin specimen. In order to test the transverse strength, transverse deflection, Young's modulus and Knoop hardness, resin specimens were processed in the manner specified in I.S.O. 1567. The data were compared the resin specimens steeped in this solution and with the control sample that was steeped in water. The specimens were immersed up to 24 hours. Furthermore the existence of tarnish was observed with a 40 times microscope. (2) metal specimen. In order to test the corrosion, metal specimens were produced according to the manner of a corrosion test. The metal specimens were held vertically and the end immersed to 20 mm in this solution for 24 hours and 120 hours each. After steeping, each specimen was measured for loss in weight. The data were calculated as the loss in weight per hour (mg/cm) and the depth of corrosion per year (mm/yr).(ABSTRACT TRUNCATED AT 400 WORDS)

Corrosion↗

Genotoxicity of a variety of hydrazine derivatives in the hepatocyte primary culture/DNA repair test using rat and mouse hepatocytes.

The genotoxicity of a variety of hydrazine derivatives was examined in the DNA-repair test on rat or mouse hepatocytes. Out of 32 hydrazine derivatives, 6 chemicals, i.e., N'-acetyl-4-(hydroxymethyl)phenylhydrazine, 1,2-dimethylhydrazine.2HCl, 1-hydrazinophthalazine.HCl, methylhydrazine.sulfate, p,p'-oxybisbenzene disulfonylhydrazide and phenylhydrazine.HCl, elicited positive DNA repair responses in the test on rat hepatocytes. In the test on mouse hepatocytes, 4 more hydrazine derivatives, i.e., 1,1-dimethylhydrazine, hydrazine hydrate, hydrazine sulfate and 2-methyl-4-chlorophenoxyacetic acid hydrazide.HCl also generated positive responses, in addition to the 6 positive compounds in the rat assay. These results suggest that mouse hepatocytes are more susceptible to the genotoxicity of hydrazine derivatives, and that the species differences in genotoxicity appear to be in agreement with the in vivo carcinogenicity of these agents.

Animals↗

Influence of ptaquiloside on the development of newborn mice.

We attempted to induce neurological disorders in mice by a single administration of various doses of ptaquiloside (PT) within 24 h after birth. Animals which survived for a long period after treatment showed a reduction in body weight, but did not develop any gait disturbance. On the other hand, in treated animals which died before beginning to walk, karyorrhexis in the external granular layer of the cerebellum and karyorrhexis and rosette formation in the neuroblastic layer of the retina were present. In addition, treated animals showed karyorrhexis and great reduction in the number of the cells in the thymus, suggesting cytotoxic and cytolytic effects of alkylating agents on lymphocytes in this organ.

Animals↗

Induction of tumors in ACI rats given a diet containing ptaquiloside, a bracken carcinogen.

Fifteen female ACI rats initially 5 weeks old were each given a diet containing 0.027-0.08% ptaquiloside [(PT) CAS: 87625-62-5], a carcinogen in bracken, throughout the 210-day experimental period. A control group of 20 female ACI rats was given basal diet without PT. Both ileal and urinary bladder tumors developed in all rats in the experimental group. The ileal tumors were multiple and mostly developed in the distal 10 cm of the ileum. These ileal tumors were identified histologically as epithelial tumors, such as adenomas and adenocarcinomas, and also as nonepithelial malignant tumors, malignant fibrous histiocytomas. The urinary bladder tumors were transitional cell carcinomas, keratinizing squamous cell carcinomas, and sarcomas. Papillomas of the urinary bladder were found in 4 rats in the control group. These results show that, like bracken diet, PT induces tumors in both the ileum and urinary bladder.

Animals↗

Reexamination of histological findings of ileal sarcomas induced in rats given diet containing bracken fern.

The ileal sarcomas induced in rats given diet containing bracken fern were examined microscopically and electron microscopically. These ileal sarcomas, which were induced at high incidence (80%-44%), have previously been identified as spindle cell fibrosarcomas. However, studies showed that they should be diagnosed as malignant fibrous histiocytomas (MFH) being classified into the following four histological types; fibrous, pleomorphic, giant cell and myxoid type. No types of sarcomas other than MFH were found in the ileum.

Animals↗

Carcinogenicity of betel quid. III. Enhancement of 4-nitroquinoline-1-oxide- and N-2-fluorenylacetamide-induced carcinogenesis in rats by subsequent administration of betel nut.

The effect of betel nut on chemical carcinogenesis in the upper digestive tract and liver was examined in two different experimental models with ACI rats. The incidences of neoplasms and preneoplastic lesions of the tongue in animals given 5 ppm 4-nitroquinoline-1-oxide (4-NQO; CAS: 56-57-5) in the drinking water for 16 weeks and followed by 20% betel nut in the diet for 40 weeks were significantly higher than those in animals given 4-NQO alone. No enhancing effect from betel nut on the incidences of neoplastic and preneoplastic lesions in the upper digestive tract was found in animals administered 4-NQO for 12 weeks. The number of altered liver cell foci in rats given 200 ppm N-2-fluorenylacetamide (FAA; CAS: 53-96-3) in the diet for 8 weeks and followed by the betel nut diet for 16 weeks was significantly greater than that in animals fed the FAA diet alone. These results indicate enhancing effects of dietary administration of betel nut on oral carcinogenesis by 4-NQO and hepatocarcinogenesis initiated by FAA.

2-Acetylaminofluorene↗

Carcinogenic principles isolated from bracken fern.

The carcinogenicity of bracken fern, Pteridium aquilinum, was demonstrated most clearly by the experiment of Evans and Mason in 1965. We have performed fractionation of the aqueous extract by means of the assay based on carcinogenicity and isolated an unstable norsesquiterpene glucoside of illudane type named ptaquiloside (PT). It was proved that PT is the carcinogenic principle present in bracken fern, inducing mammary cancer and multiple ileal tumors in high incidences when given orally to female Sprague-Dawley rats. The present review article deals with the explanation of carcinogenicity of bracken fern, progress in separation of carcinogenic fraction, isolation of PT, and its carcinogenic activity in rats.

Animals↗

Carcinogenicity of chrysazin in large intestine and liver of mice.

The carcinogenicity of chrysazin (1,8-dihydroxy-9,10-anthracenedione) was examined by dietary administration to C3H/HeN mice. All of the effective mice (17) which were given 0.2% chrysazin diet and which survived more than 500 days developed adenomatous hyperplasia with cystic glands of the cecum. Similar lesions were also seen in the colon of mice in this group. These intestinal lesions were not obtained in any effective mouse (19) of the control group. The incidence of hepatocellular carcinoma of mice given chrysazin (4/17) was significantly higher than that of the controls (0/19). These results indicate that chrysazin is carcinogenic in mice as well as in rats. Some mechanistic aspects of the causation of these intestinal lesions and liver neoplasms are also discussed.

Animals↗

Absence of initiating activity by quercetin in the rat liver.

Initiating activity of quercetin was tested in rats which were treated with partial hepatectomy and given a liver cancer promoter, phenobarbital. A few intestinal neoplasms were seen but without significant difference in incidence from those in the quercetin-untreated group. Moreover, neither neoplastic nor preneoplastic liver changes were detected in quercetin-treated groups. With hepatocyte primary culture/DNA repair test, quercetin did not produce genotoxicity. The results show that quercetin has no initiating or genotoxic activities in the rat liver.

Animals↗

Human carcinogenic risk in the use of bracken fern.

Young bracken fern is used as a human food in Japan and other countries. However, it has been demonstrated that bracken is carcinogenic to cattle and laboratory animals such as rats, mice, and guinea pigs. Rats fed a diet containing bracken fern developed tumors of the ileum and urinary bladder. Mammary cancer was also induced in Sprague-Dawley rats fed a bracken diet. Study of the human cancer risk of this plant is thus of great importance. The fern is usually used as a food-stuff in Japan after it is treated with plain boiling water or boiling water containing wood ash or sodium bicarbonate; sometimes, bracken is pickled in salt. Although the carcinogenic activity of processed bracken thus prepared was reduced markedly, weak activity was still retained. This paper deals with the carcinogenicity of unprocessed and processed bracken fern to laboratory animals and its human cancer risk.

Animals↗