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Biomedical subjects

M Ishidate

Publications and source records attributed to M Ishidate.

At least 109 records · Page 6Linked to original sources
PubMed1979

Chromosomal aberration tests on 29 chemicals combined with S9 mix in vitro.

A metabolic activation system with rat-liver microsome fraction plus cofactors (S9 mix) was applied to chromosomal aberration tests in vitro for the screening of chemical mutagens or carcinogens in the environment. Dialkylnitrosamines only induced chromosomal aberrations in Chinese hamster cells (CHL) when treated with S9 mix. The incidence of chromosomal aberrations in CHL varied with experimental conditions, e.g. incubation time, recovery time, components of S9 mic and inducers used for preparation of S9. For dimethylnitrosamine (DMN), the maximal incidence was obtained when the cells were incubated with S9 mix for 3 h and harvested 24 h after treatment. Therefore, this system (3 h incubation and 24 h recovery) was routinely applied to further screening of other chemicals with S9 prepared from PCB-pretreated rats. 10 carcinogens (e.g. 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene, quinoline, etc.) out of 16 induced aberrations when they were treated with S9 mix, whereas the remaining 6 carcinogens (e.g., 3-methyl-cholanthrene, 4-o-tolylazo-o-toluidine, etc.) induced few or no aberrations even after activation. Two insecticides, allethrin and diazinon, were strongly positive at relatively low doses only when they were activated with the S9 mix. Medical drugs, such as ethenzamide, methyl p-hydroxybenzoate and nitrofurazone, and a food additive, sodium hypochlorite, were positive on activation. Chemicals used for industry, such as styrene monomer and tris-dichloropropylphosphate, were also positive in our activation system.

Animals↗
PubMed1979

Differential mutagenicities of triamino benzenes against Salmonella typhimurium TA98 in the presence of S9 fractions from polychlorinated biphenyls-, phenobarbital- or 3-methylcholanthrene-pretreated rats, hamsters and mice.

Mutagenicity of 6 aminobenzene derivatives against Salmonella typhimurium TA98 was studied in the presence of various S9 fractions. S9, which has been prepared form the livers of rats, hamsters and mice after pretreatment with different types of inducers; polychlorinated biphenyls, phenobarbital and 3-methylcholanthrene, was used as the methabolic activating enzyme in this mutation assay. The S9 fractions from 3-methylcholanthrene-treated rats and mice are most useful for mutation induction by the all aminobenzenes used. The mutagenic activity of the compounds was clearly correlated to 3-methylcholanthrene-induced cytochrome P-450. However, any significant correlation between aniline hydroxylase activity and the mutagenesis was not observed.

Aniline Hydroxylase↗
PubMed1978

Colchicine-like effect of diethylstilbestrol (DES) on mammalian cells in vitro.

Diethylstilbestrol (DES), a synthetic estrogen, showed colchicine-like effects in vitro on cells of the cell lines such as Chinese hamster fibroblast of thymus origin (CHT), rat liver (DL), rat erythroblastic leukemia (EDEN-1/TC) and HeLa-S3. Metaphase arrest was induced 3 h after treatment with 15 microgram/ml of DES and polyploid or polynucleated cells were prominently observed more than 24 h after treatment. The arrest, however, was reversible when the agent was removed from the medium. Tetraploid karotypes induced by DES in CHT cells consisted of all double sets of diploid chromosome constitution except one chromosome marker. By clonal selection, several hypotetraploid sublines were successfully isolated from a CHT cell population after the treatment with 15 microgram/ml of DES for 48 h. Some comparative studies of cytological effects of DES with those induced by colcemid indicated that the DES effect was also a mitotic inhibition similar to colchicine.

Aneuploidy↗
PubMed1977

Chromosome tests with 134 compounds on Chinese hamster cells in vitro--a screening for chemical carcinogens.

Chromosomal aberration tests in vitro were carried out on Chinese hamster cells grown in culture with various chemicals, including carcinogenic N-nitroso compounds and their related derivatives, food additives, medical drugs, pesticides and other chemicals commonly used in laboratories or industries. Sixty-three of the 134 chemicals gave negative results in our test system even with doses at which the cell growth was markedly inhibited. Nearly all compounds known to be mutagenic in bacteria were also positive in our tests. Both urethane and diethylstilbestrol were positive, even though they are known to be carcinogenic but not mutagenic in bacteria. Compounds such as N-alkyl-N'-nitroguanidines, barbital, sodium benzoate, saccharin sodium, sodium nitrite, sodium nitrate and 4-aminoquinoline-1-oxide were positive in our chromosome tests, but they have not been conclusively tested for their carcinogenicity.

Animals↗
PubMed1977

Antitumor effect of 1,1'-polymethylene-bis (1-nitrosourea) and related compounds.

Polymethylene-bis(1-nitrosourea), polymethylene-bis(1-nitroso-3-nitroguanidine), and polymethylene-bis(1-nitroso-p-toluenesulfonamide) derivatives were tested for antitumor effect against rat ascites hepatoma AH-13 and mouse leukemia L-1210. Bisnitrosoureas were effective against AH-13 and L-1210, bisnitrosoguanidines were effective against AH-13 alone, and bisnitrosotoluene-sulfonamides were ineffective against both tumor lines. Of all these compounds, 1,1'-ethylene-bis(1-nitrosourea) (EBNU) was the most effective. The antitumor effect of EBNU was compared with that of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Intraperitoneal administration of EBNU according to the schedule, day 1, days 1 and 5, and days 1, 5, and 9 after intraperitoneal inoculation of L-1210 showed marked prolongation of host survival, although the effective doses used were a few times higher than those used in BCNU to obtain a similar effect. The minimum effective dose (MED) of EBNU on AH-13 cells was estimated as 1 mg/kg, which was 10 times less than that of BCNU, suggesting that EBNU was more effective than BCNU against AH-13.

Animals↗
PubMed1976

Alteration of biologic behavior of a rat leukemia by different routes of passage.

Two clonal leukemia cell lines exhibiting diploidy or tetraploidy were isolated separately from a mother cell population of rat myelogenous leukemia DBLA-6 (induced by 1-butyl-1-nitrosourea), and their biologic characteristics altered during serial iv or ip passages in Donryu rats were examined. In early generations after the establishment of the clones, leukemia-inducing capacities were clearly demonstrated only in the diploid clone and were characterized as follows: a) release of leukemia cells into the peripheral blood after inoculation, and b) infiltration, and growth of leukemia cells in the bone marrow and spleen. After repeated iv passages, however, leukemia-inducing capacity was greater not only in the diploid but also in the tetraploid clone. By serial ip passages, this capacity was never acquired but was gradually lost even in the diploid clone. Cell electrophoretic mobility, cell size, or susceptibility to chemotherapeutic agents were also modified. There was a strong correlation between the routes of passage and the direction of the changes: The iv route enhanced or the ip route suppressed the leukemia-inducing capacity. Chromosome constitutions were also changed.

Alkylating Agents↗
PubMed1975

A tumor-specific cytotoxic and neutralizing factor in rats immunized with ascites hepatoma induced by azo dyes.

Transplantation immunity of Donryu rats against ascites hepatoma AH-64A induced by azo dye was demonstrated by intraperitoneal injection of tumor cells pretreated with heteroantibodies in vitro. Hyper-immunity was induced by successive challenges with fresh tumor cells. The cytotoxic effect of the serum of resistant rats (RRS) against AH-64A tumor cells was not reduced after absorption with normal rat liver cells, but was slightly reduced after absorption with normal rat spleen cells. The cytotoxicity was absorbed completely with 5 times 10(6) AH-64A tumor cells. AH-64A, -B, -C, and -D are ascites hepatoma cell lines originating from a single Donryu rat. AH-64A and AH-64B cross-reacted with RRS while AH-64C and AH-64D, chemically induced DBLA-6 leukemia cells and normal lymph node cells of rats, did not react with RRS in indirect immunofluorescence and cytotoxicity tests. A neutralization test was carried out by treating 2 times 10(5) tumor cell with either RRS or immune spleen cell in vitro and then injecting them subcutaneously into irradiated rats (400 R). It was found that 1:20 dilution of RRS protected the rats against AH-64A tumor cell growth while 1:40 and 1:80 dilutions of RRS caused some protection. A subcutaneous tumor mass developed after transplantation of tumor cells treated with RRS, but after about 2 weeks this began to decrease in size and disappeared completely within 6 weeks after transplantation. Treatment of AH-64A tumor cells with immune spleen cells at cell-to-cell ratios of 1:200 and 1:100 caused complete neutralization while normal spleen cells at a ratio of 1:200 had slight effect. Treat;ent with immune spleen cells prevented tumor growth from t;e start. Most of the surviving animals were resistant to c,allenge with 1 times 10(5) fresh AH-64A cells. RRS was fractionated by cellulose acetate membrane electrophoresis and the amounts of beta1- and gamma-globulin fractions were found to be 48 and 42% more than in normal rat serum. The immunoelectrophoretic pattern of resistant rat serum showed a stronger IgM precipitin line than that of normal rat serum.

Animals↗