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Biomedical subjects

N Inui

Publications and source records attributed to N Inui.

At least 73 records · Page 4Linked to original sources
PubMed1985

Histidine increases the frequency of chromosomal aberrations induced by the xanthine oxidase-hypoxanthine system in V79 cells.

The combined effects of the xanthine oxidase (XO)-hypoxanthine (HX) system and the various kinds of amino acids in Eagle's minimum essential medium on chromosomal aberrations were studied in Chinese hamster V79 cells. Among 13 amino acids tested, only histidine significantly increased the number of aberrant chromosomes and cytotoxicity in combination with the XO-HX system. This enhancing effect of histidine on chromosomal aberrations was dose-dependent at 0.063% - 0.25%; it was not affected by superoxide dismutase, but was strongly inhibited by catalase.

Animals↗
PubMed1984

Forward mutation assay of V79 cells to 6-thioguanine resistance in a soft agar technique that eliminates effects of metabolic co-operation.

A technique involving culture in soft agar was used for the assay of forward mutation of V79 cells to 6-thioguanine (6TG) resistance. The main reason for the use of soft agar was to prevent reduction in recovery of mutants depending on the cell density plated for mutation selection, which is the chief problem in the liquid method, and which results mainly from metabolic co-operation due to cell-to-cell contact. V79 cells grew well in fortified soft agar medium (DMEM + 20% FBS) showing cloning efficiencies (greater than 80%) as high as in liquid culture. Therefore, V79/HGPRT mutagenesis could be assayed quantitatively in soft agar culture. The frequency of 6TG-resistant colonies in agar selective medium increased linearly with increase in concentration of EMS. Toxicity and mutagenic responses were greater in soft agar than in liquid culture. In cultures of untreated and EMS-treated cells, more than 95% of the 6TG-resistant colonies isolated were aminopterin-sensitive. Use of soft agar for selection prevented the reduction in the number of mutants with increase in the size of inocula on plating up to 1-2 X 10(6) cells per 9-cm dish: in liquid culture, even with a lower plating number (2 X 10(5) cells per 9-cm dish), a notable reduction in numbers of mutants was observed. This character was re-examined in a reconstruction experiment. The results show that, when up to 2 X 10(6) cells were plated per 9-cm dish, 6TG-resistant cells were almost completely recovered from the soft agar medium, whereas only 10% were recovered from liquid culture.

Animals↗
PubMed1984

Effects of sorbic acid and its salts on chromosome aberrations, sister chromatid exchanges and gene mutations in cultured Chinese hamster cells.

The ability of sorbic acid and its potassium and sodium salts to induce chromosome aberrations, sister chromatid exchanges (SCE) and gene mutations in cultured Chinese hamster V79 cells was examined. Sodium sorbate caused significant induction of chromosome aberrations and SCE, and also induced 6-thioguanine-resistant mutations in a dose-dependent manner. The clastogenic potency of sodium sorbate was found to be less than one hundredth of that of the potent clastogen N-methyl-N'-nitro-N-nitrosoguanidine. The induction of SCE by sodium sorbate was twice the control level, whereas that by methyl methanesulphonate, a potent inducer of SCE, was 14 times the control level. The mutagenic potency of sodium sorbate was less than one-tenth that of ethyl methanesulphonate, a potent inducer of mutation, when compared at an equitoxic level. Sorbic acid and its potassium salt induced chromosome aberrations, but only at the highest doses tested. These compounds also induced 1.2 times the control level of SCE, but neither compound induced 6-thioguanine-resistant mutations. The cytogenetic activity of sodium sorbate was concluded not to be due to the effect of osmotic pressure or an impurity. These results indicate that sodium sorbate is a genotoxic agent, although its potency seems to be weak, and that sorbic acid and potassium sorbate are less genotoxic than the sodium salt.

Animals↗
PubMed1984

A rapid, simple screening method for skin-tumor promoters using mouse peritoneal macrophages in vitro.

The enhancing effects in vitro of a potent skin-tumor promoter, phorbol myristate acetate (PMA), and its derivatives on nitroblue tetrazolium (NBT) reduction, phagocytosis and cell spreading of mouse peritoneal macrophages were compared. The enhancing effects on these markers of macrophage function, especially NBT reduction, were found to correlate well with the skin-tumor promoting activities of the phorbol esters. Another potent promoter, teleocidin, strongly enhanced NBT reduction, although teleocidin is structurally different from phorbol esters. Other tumor promoters, namely saccharin, phenobarbital, cantharidin and Tween 60 did not enhance NBT reduction by macrophages. These data indicate that this test system is appropriate for screening of PMA-type tumor promoters such as phorbol esters and teleocidin.

Animals↗
PubMed1984

Chromosomal aberrations in V79 cells induced by superoxide radical generated by the hypoxanthine-xanthine oxidase system.

The effect of the superoxide radical, generated by the hypoxanthine-xanthine oxidase system, on chromosomal mutation was examined in Chinese hamster V79 cells. When cells were treated with this system for 1 h in Hanks' solution, the incidence of metaphases with chromosomal aberrations was increased with hypoxanthine at concentrations of 2.5 to 10 micrograms/ml. On the other hand, in Eagle's minimum essential medium (MEM) or MEM supplemented with 10% fetal bovine serum, only hypoxanthine at 5 micrograms/ml plus xanthine oxidase induced chromosomal aberrations and higher concentrations of hypoxanthine were cytotoxic to V79 cells. The increased frequency of chromosomal aberrations and the cytotoxicity of hypoxanthine plus xanthine oxidase were not affected by superoxide dismutase, but were strongly inhibited by catalase.

Animals↗
PubMed1984

Comparison of 6-thioguanine-resistant mutation and sister chromatid exchanges in Chinese hamster V79 cells with forty chemical and physical agents.

The induction of sister chromatid exchanges (SCE) and mutation at the hypoxanthine-guanine phosphoribosyl transferase locus and toxicities of 40 different chemical and physical agents were examined on Chinese hamster V79 cells. These agents included mono-, di-, tri-, and polyfunctional alkylating agents, intercalators, gamma-rays, and UV light irradiation. Mutation was measured as resistance to 6-thioguanine and toxicity as loss of cell-plating efficiency. SCE were examined 29 hr after treatment. With the agents examined, a highly positive correlation (r = 0.89) existed between SCE-inducing and mutagenic potencies, when expressed as increase in the number per a unit dose over the control values. But the great difference of the ratios of mutagenic potencies versus SCE-inducing potencies among agents was observed, the maximal difference in the ratios being about 200-fold. The agents that showed the higher values of the ratio (agents producing more mutations than SCE) were bleomycin, cobalt-60 gamma-rays, all ethylating agents (N-ethyl-N-nitrosourea, N-ethyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, and diethylsulfate), N-propyl-N-nitrosourea, N-butyl-N-nitrosourea, isopropyl methanesulfonate, intercalating acridine compounds (2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)aminopropylamino]-acridine X 2HCl and 2-methoxy-6-chloro-9-[3-(chloroethyl)-aminopropylamino]acridine 2HCl) and UV light at 254 nm. The agents that showed the lower values (agents producing more SCE than mutations) were platinum compounds (cis-diamminedichloro-platinum and trans-diamminedichloroplatinum), epoxides (epichlorohydrin, styrene oxide, and diepoxybutane) and aziridines (mitomycin C, decarbamoyl mitomycin C, tris(1-aziridinyl)phosphine sulfide, triethylenemelamine, and carboquone). The agents that showed the intermediate values included all methylating agents (N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine, methyl methanesulfonate, and dimethyl sulfate), N-(2-hydroxyethyl)ethyleneimine, beta-propiolactone, treatment of 8-methoxypsoralen plus near-UV light irradiation at 352 nm, 4-nitroquinoline-1-oxide, quinacrine mustard, sodium sorbate, cigarette tar, and diesel tar. For most agents that induced SCE, the toxicity dependency of induced SCE was rather biphasic; increase in SCE was steep at low to moderate toxicity and less at moderate to high toxicity. At equitoxic doses, the agents showed great difference in induction of SCE.

Animals↗
PubMed1983

Increase during passage in culture in susceptibility of Syrian hamster embryonic cells to induction of chromosome aberrations by 7,12-dimethylbenz(a)-anthracene.

Studies were made on chromosome aberrations in Syrian hamster embryonal fibroblasts (SHEF) at early and late passages in culture. Aberrations were induced with a potent indirect clastogen, 7,12-dimethylbenz(a)anthracene (DMBA). Results showed that cells at late passages were much more susceptible to this chemical than cells at early passages: the frequency of aberrant metaphases was usually less than 20% at the 2nd passage, but it gradually increased with increase in the number of culture passages, reaching 50% or more at the 8th passage in one experiment and 6th-7th passage in another. Induction of chromosome aberrations was also examined in V79 cells co-cultured with hamster cells at early and late passages. V79 cells are known to have no drug-metabolizing enzyme activity. Results demonstrate that the frequency of chromosome aberrations of V79 cells was much greater in the presence of hamster cells at late passages than in the presence of cells at early passages.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Mutagenic/carcinogenic potential of DEHP and MEHP.

The mutagenic/carcinogenic activities of DEHP and MEHP were studied in bacteria and mammalian cells. MEHP but not DEHP exerted a dose-dependent DNA damaging effect to B. subtilis in Rec-assay. DEHP and MEHP showed mutagenic activities to S. typhimurium TA-100, with and without S-9 mix, respectively. MEHP produced not only the mutation in E. coli WP2B/r but also sister chromatid exchanges (SCE) in Chinese hamster V79 cells. It also induced 8AG/6TG-resistant gene mutations and chromosomal aberrations in the V79 cells. Transplacental administration of DEHP or MEHP to the Syrian golden hamster embryos was carried out by administering DEHP or MEHP to gravid animals on day 11 of gestation, followed by the cultivation of embryonic cells for 15-20 days. Both DEHP and MEHP induced 8AG/6TG-resistant mutation, chromosomal aberrations and morphological transformation in the embryonic cells of the Syrian golden hamster.

Animals↗
PubMed1981

Induction of active melanocytes in mouse skin by carcinogens: a new method for detection of skin carcinogens.

Application of potent skin carcinogens, such as 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, benzo[a]pyrene and 4-nitroquinoline-1-oxide, induced numerous dihydroxyphenylalanine (dopa)-positive cells in the interfollicular epidermis of C57BL/6 mice in a dose- and time-dependent fashion. Chrysene, a weak skin carcinogen, and croton oil, a tumor promoter, also induced 3--4 times more dopa-positive cells than acetone. Liver carcinogens, such as 3'-methyl-4-dimethylaminoazobenzene and N-2-acetylaminofluorene, and non-carcinogenic aromatic hydrocarbons, such as anthracene, fluoranthene, fluorene and pyrene, did not induce increase in these cells. These results indicate that increase in the number of dopa-positive cells after application of chemicals is well correlated with the abilities of these compounds to induce skin carcinogenesis and suppress sebaceous glands.

Animals↗
PubMed1980

Induction of 8-azaguanine-resistant mutation and neoplastic transformation of hamster embryonic cells by coadministration of sodium nitrite and aminopyrine.

Hamster embryos in utero on the 11th or 12th day of gestation were treated simultaneously with aminopyrine (Ap) and sodium nitrite (NaNO2) by oral administration of the compounds to the mothers by stomach tube. For measurement of induction of 8 AG-resistant mutations, the embryonic cells from treated and control mothers were cultured in MEM plus 10% FBS for 72 h and then selected in medium containing 10 or 20 microgram/ml of 8 AG. The number of 8 AG-resistant colonies was markedly increased after co-administration of Ap and NaNO2, and slight induction of mutations was also observed in cells from mothers given NaNO2 alone. This treatment also caused morphological or malignant transformation of cultured cells. About 5- to 6-fold increase in the number of transformed colonies was observed in cells from mothers given Ap plus NaNO2. Cells from the transformed colonies produced tumors when implanted into the cheek pouches of young golden hamsters. These tumors were diagnosed as pleomorphic fibrosarcomas. Similar results were obtained with cells from embryos treated transplacentally with NDMA as positive controls. A single transplacental oral application of Ap at 200 mg/kg or of NaNO2 had only slight biological actions to the cultured embryonic cells. NDMA was produced in the stomach of animals treated simultaneously with Ap and NaNO2. A small amount of NDMA was also detected in the stomach after a single dose of NaNO2.

Abnormalities, Drug-Induced↗
PubMed1980

Comparative studies on chromosome aberrations induced by polycyclic hydrocarbons in cell-mediated and microsome-mediated assay.

Studies were made on chromosome changes in Chinese hamster V79 cells induced by the polycyclic hydrocarbons, benzo[alpha]pyrene (BP), 3-methylchol-anthrene (MC) and 7,12-dimethylbenz[alpha]anthracene (DMBA) in the presence and absence of cell-mediated and microsome-mediated activation systems. In cell-mediated assay, BP, MC and DMBA induced concentration-dependent chromosome aberrations in V79 cells, at concentrations of 0.5--1.0 to 10.0 micrograms/ml in the presence of lethally irradiated Syrian hamster embryonal feeder cells at 2.0 X 10(6) cells/60-mm dish. The highest incidences of cells with aberrant chromosomes, observed at concentrations of 20 micrograms/ml, were 24.0% (BP), 23.0% (MC) and 80.0% (DMBA). In the absence of feeder cells, these chemicals did not induce chromosome aberrations in V79 cells, even at the maximum concentrations tested, only background levels being observed. In microsome-mediated assay, BP, MC and DMBA at 20 micrograms/ml also induced chromosome aberrations when combined with microsomes. However, the highest incidences of aberrations were observed with lower amounts of microsomes than usual, the optimal amount of microsomes ranging from 1 to 10%. In this range, the highest incidences of cells with aberrant chromosomes were 10.0% (BP), 9.0% (MC) and 28.0% (DMBA), that is about half to one-third those observed in cell-mediated assay.

Animals↗
PubMed1980

Induction of 8-azaguanine or ouabain resistant somatic mutation of Chinese hamster lung cells by treatment with tryptophan products.

The basic fraction of tryptophan pyrolysis products (TBF) showed strong mutagenic activity on somatic cells of the lung of Chinese hamsters. In this somatic mutation test, TBF was demonstrated to have 5.6 times higher mutagenicity than diethylnitrosamine (DEN) when mutants were selected with 8-azaguanine, and 13.5-fold higher mutagenicity than DEN when mutants were selected with ouabain. From these findings, it is suggested that pyrolyzates of amino acids may have mutagenic actions on somatic cells of animals, as well as carcinogenic actions.

Animals↗
PubMed1980

Formation of a transplacental mutagen, 1,3-Di(4-sulfamoylphenyl)triazene, from sodium nitrite and sulfanilamide in human gastric juice and in the stomachs of hamsters.

1,3-Di(4-sulfamoylphenyl)triazene was abundantly produced by incubation of sulfanilamide (SA) and NaNO2 in human gastric juice. This reaction also occurred in acetate buffer (pH approximately 4) at 37 degrees C as well as in hydrochloric acid (pH < 1) under ice cooling, with the product forming in almost the same amount. This phenomenon indicated the broad range of conditions under which the reaction occurs. The intragastric formation of this triazene was also demonstrated in Syrian golden hamsters by the concurrent administration of SA and NaNO2. Mutants resistant to 8-azaguanine were induced in a dose-dependent manner in the culture of embryo cells that were derived from pregnant hamsters 24 hours after ip injection of this triazene.

Animals↗
PubMed1979

Transplacental mutagenesis of products formed in the stomach of golden hamsters given sodium nitrite and morpholine.

Hamster embryos were exposed in utero to the action of sodium nitrite (NaNO2) and morpholine (Mo) administered simultaneously by stomach tube to the mothers on the 11th or 12th day of pregnancy. Embryo cells were examined for chromosomal aberrations, micronuclear formation, morphological or malignant transformation and drug resistance mutations. For detection of induced mutations, the embryo cells were cultured in normal medium for 72 h and then transferred to medium containing 10 or 20 micrograms/ml of 8-azaguanine (8AG) or 1m7 ouabain (Oua). The number of 8AG-, Ouaresistant colonies was markedly increased after administration of NaNO2 and Mo. The embryonic fibroblasts also showed a markedly increased frequency of micronucleation and a slight increase in chromosome aberrations. This treatment also caused morphological or malignant transformation of fetal cells. After cultivation in vitro, cells from some transformed colonies produced tumors when inoculated into the cheek pouch of young golden hamsters. Orally administered N-nitroso-morpholine (N-Mo), as a positive control, had the same transplacental biological actions on embryonic fibroblasts. However, transplacentally Mo alone was ineffective. A single administration of 500 mg/kg NaNO2 had only slight biological effects. N-Mo was produced in the stomachs of animals treated simultaneously with NaNO2 and Mo. A small amount of a nitrosamine, N-nitrosodimethylamine (DMN), was detected in the stomach after a single dose of NaNO2.

Animals↗