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Biomedical subjects

M Ishidate

Publications and source records attributed to M Ishidate.

At least 73 records · Page 4Linked to original sources
PubMed1987

Cytogenetic studies on 1,1-dichloroethylene and its two isomers in mammalian cells in vitro and in vivo.

Chromosomal aberration and sister-chromatid exchange (SCE) tests in vitro on 1,1-dichloroethylene (1,1-DCE), its two isomers, cis- and trans-1,2-DCE, and two possible metabolites of 1,1-DCE, chloroacetyl chloride and chloroacetic acid, were carried out using a Chinese hamster cell line, CHL. 1,1-DCE induced chromosomal aberrations in the presence of S9 mix prepared from the rat liver, but not in the absence of S9 mix. SCEs were also slightly induced by 1,1-DCE only in the presence of S9 mix. On the other hand, two isomers and two metabolites of 1,1-DCE induced neither chromosomal aberrations nor SCEs with and without S9 mix. 1,1-DCE, however, was negative even at a sublethal dose in the micronucleus test using mouse bone marrow, fetal liver and blood.

Animals↗
PubMed1987

Chronic toxicity of charred fish meat in Wistar rats.

An experiment was performed on Wistar rats to examine the possible carcinogenic effects of charred fish meat. Each group (of 30 male rats each) was fed one of the following diets: the standard diet mixed with 50% charred fish meat (Group 1), the standard diet mixed with 25% charred fish meat (Group 2), the standard diet alone (Group 3), or the 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) treatment in drinking water (Group 4); this last group served as positive control. The animals were observed for two years. No significant incidences of tumors were recorded. However, there were statistically significant incidences of nonspecific pathological lesions of the glandular stomach, such as erosion, regeneration, and hyperplastic epithelium. Also, an atypical epithelium of the stomach was found incidentally in two animals (Groups 1 and 2); this might suggest a premalignant condition.

Animals↗
PubMed1987

Metabolic activation of phenacetin and phenetidine by several forms of cytochrome P-450 purified from liver microsomes of rats and hamsters.

Metabolic activation of phenacetin by liver microsomes proceeds via both phenetidine and N-hydroxyphenacetin to direct-acting mutagens, i.e., N-hydroxyphenetidine and p-nitrosophenetole. Five different molecular species of cytochrome P-450 have been purified from liver microsomes of drug-pretreated Wistar rats or Syrian hamsters and their abilities to activate phenetidine and phenacetin were compared using reconstituted microsome systems. High-spin forms of cytochrome P-450 purified from 3-methylcholanthrene-pretreated rats (MC-P-448-H) or hamsters (P-488 ham-II) showed higher catalytic activity for N-hydroxylation of phenetidine than three other low-spin forms of cytochrome P-450 purified from the same animals or from phenobarbital-pretreated rats. MC-P-448-H and P-488 ham-II required the presence of cytochrome b5 for their maximum activities in the reconstituted system. The five forms of cytochrome P-450, however, exhibited no measurable activity for N-hydroxylation of phenacetin either with or without cytochrome b5. The mutagenicity of phenacetin and phenetidine toward Salmonella typhimurium TA100 was generated when the reconstituted microsomes containing MC-P-488-H or P-488 ham-II were used as activating enzymes. From these results, it was suggested that high-spin forms of cytochrome P-450 (MC-P-448-H and P-448 ham-II) played an important role in the metabolic activation of phenacetin to the direct-acting mutagens.

Aminophenols↗
PubMed1986

Clastogenicity in vitro of the Na, K, Ca and Mg salts of saccharin; and of magnesium chloride; consideration of significance.

The sodium, potassium, calcium and magnesium salts of saccharin, and magnesium chloride, have been shown to be clastogenic to Chinese hamster lung (CHL) fibroblasts in vitro, but only at elevated dose levels (8-16 mg/ml). Saccharin acid was inactive to the limits of its solubility (4 mg/ml). When the data are expressed in terms of ionic concentration, each salt showed a similar clastogenic potency. This suggests that ionic effects induced by these salts in the assay medium may be the critical determinant of the clastogenic effects seen, rather than that the saccharin moiety presents a genotoxic insult to the chromosomes of the cells. The metal-chelating agents EDTA and EGTA were non-clastogenic, but the disodium salt of EDTA showed weak activity prior to toxicity at 0.5 mg/ml. The absence of a clastogenic response for the salts of saccharin at dose levels lower than 4 mg/ml is discussed within the context of the threshold-dependent tumour-promoting activity of high dose levels of sodium saccharin to the bladder of male rats. The doubtful value of conducting in vitro clastogenicity studies at dose levels greater than 10(-2) M is discussed.

Animals↗
PubMed1986

Production of restriction endonucleases using multicopy Hsd plasmids occurring naturally in pathogenic Escherichia coli and Shigella boydii.

A convenient procedure has been devised for detection of restriction endonucleases in the Escherichia coli-Shigella group. With this procedure, two restriction endonucleases, designated Sbo 13 and Eco T22, were found and later were identified as isoschizomers of NruI and AvaIII, respectively. These endonucleases were shown to be produced from small multicopy plasmids. They were isolated from nonpathogenic E. coli into which the plasmids had been introduced by transformation, and purified from contaminating nuclease activity. The yield was high, 1,000 units/g of wet cells for Sbo 13 and 500 units/g for Eco T22. Sbo 13 and Eco T22 should be preferable to NruI and AvaIII because of the high yield and ease in handling the producer cells.

DNA Restriction Enzymes↗
PubMed1984

Kinetics of micronucleus formation in relation to chromosomal aberrations in mouse bone marrow.

A simulation analysis of the kinetics of micronucleus formation in polychromatic erythrocytes in mouse bone marrow was performed after a single administration of 3 chemicals--mitomycin C (MMC), 6-mercaptopurine (6-MP) and 1-beta-D-arabinofuranosylcytosine (Ara-C)--with different modes of action. The time-response patterns in the incidence of chromosomal aberrations and micronuclei after treatment with each chemical were compared and subjected to the simulation study with 3 parameters. Two of them, the time between the final mitotic metaphase of the erythroid series and nucleus expulsion (T1), and the duration of the polychromatic erythrocyte (PCE) stage in the bone marrow (T2), were almost identical for the 3 chemicals. However, the coefficients of formation rate of micronucleated cells resulting from cells with chromosomal aberration(s) (k) differed: Ara-C differed from the other two. These results indicate that chromosomal aberrations, especially chromatid breaks and probably gaps, induced by this chemical, effectively contribute to micronucleus formation. The DNA content of micronuclei was also compared to the length of acentric fragments induced by Ara-C and it was found that their distributions were comparable. These findings strongly suggest that chromosomal aberrations induced by chemicals are essential events for the induction of micronuclei in the PCE of bone marrow.

Animals↗
PubMed1984

Mutations in Salmonella typhimurium and inactivation of Bacillus subtilis transforming DNA induced by phenylhydroxylamine derivatives.

Phenylhydroxylamine (PHA) and its derivatives such as monomethyl (2-Me, 3-Me, 4-Me) and dimethyl (2,3-diMe, 2,4-diMe, 2,5-diMe, 2,6-diMe, 3,4-diMe, 3,5-diMe) were tested for their mutagenicity and for their inducing ability to inactivate transforming DNA. All these compounds except PHA and 3,5-diMePHA were found to be mutagenic in Salmonella typhimurium TA100 even in the absence of S9 mix, and their mutagenic potency was in the order: 2,6-diMe- greater than 2,4-diMe- = 3,4-diMe- greater than 4-Me- greater than 2,3-diMe- = 2,5-diMe- greater than 2-Me- = 3-MePHA. Besides mutagenicities, all the PHA derivatives except 2,6-diMePHA caused severe reductions in the activity of Bacillus subtilis transforming DNA. To establish the structure-activity relationship, we examined the correlation between these activities and the stabilities of the PHA derivatives, and the results indicated that the more chemically unstable the PHA derivatives were, the more active they were with respect to the mutations and to the inactivation of the transforming DNA. The mutagenic activity of 2,6-diMePHA was the sole exception, because it was most stable, but its induced mutation frequency was highest. From these results, we suggest that all the PHA derivatives, except 2,6-diMePHA, cause DNA damage through the generation of active molecular species, such as nitrenium ions, without any enzymatic activation, while 2,6-diMePHA requires further metabolic activation by bacterial enzymes to stimulate mutagenesis.

Animals↗
PubMed1984

Induction of chromosomal aberrations in cultured Chinese hamster cells in a superoxide-generating system.

The induction of chromosomal aberrations in a superoxide-generating system using xanthine oxidase and hypoxanthine was investigated in cultured Chinese hamster cells. The production of chromosomal aberations in this system was inhibited by the addition of cytochrome C. This finding indicates that the generation of superoxide was the primary requirement for induction of chromosomal aberrations. On the other hand, superoxide dismutase showed no effect on the frequency of chromosomal aberrations, whereas catalase was effective in preventing the aberrations. It is conceivable, therefore, that the induction of chromosomal aberrations in the superoxide-generating system may be directly or indirectly due to hydrogen peroxide formed in the cultured medium as a result of the spontaneous dismutation reaction of superoxide.

Animals↗