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Biomedical subjects

M Ishidate

Publications and source records attributed to M Ishidate.

151 records · Page 9Linked to original sources

Micronucleus test on quinacrine dihydrochloride in mice: a comparison of dosage regimens.

Micronucleus induction by quinacrine dihydrochloride (Q) was tested in CD-1 male mice by single, double, and triple oral treatment(s) with 50 or 250 mg/kg. The mice were killed 24 h after the last treatment. Femoral marrow cells were analyzed on slides stained with Giemsa and acridine orange. Both staining methods gave similar results. The frequencies of micronucleated polychromatic erythrocytes (MPE) were marginally increased, in comparison with a concurrent negative control group, only in the triple treatment group of 250 mg/kg. There were, however, no big differences in MPE frequencies among the treatment regimens.

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Multiple-dosing effects of benzo[a]pyrene in the mouse bone marrow micronucleus test.

Multiple-dosing effects of benzo[a]pyrene (B[a]P) in the micronucleus test were studied using CD-1 male mice. Mice were treated orally once, twice or 3 times with 250, 500, 1000 or 2000 mg/kg, at 24-h intervals. Bone marrow cells were sampled 24 h after the last administration. The present study indicated that the incidence of polychromatic erythrocytes with micronuclei significantly increased more in the group of animals that received B[a]P twice than in those receiving it one or 3 times. The dose of 500 mg/kg B[a]P yielded the greatest response of any dose regimen.

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Clastogenic potential of heavy oil extracts and some aza-arenes in Chinese hamster cells in culture.

Chromosomal aberration tests in vitro, with a Chinese hamster fibroblast cell line, CHL, were carried out on B class heavy oil fractions, obtained by silica-gel column chromatography and a liquid-liquid extraction method. The original oil and basic nitrogen-containing fractions induced structural chromosomal aberrations in the CHL cells in the presence of rat-liver microsome fraction (S9 mix). 8 tricyclic or pentacyclic aza-arenes, which possibly exist in the positive fractions, were also examined for their clastogenic activities in the system with or without S9 mix. Acridine, benzo[f]quinoline, pyrenoline and pyrenoline 4,5-oxide induced chromosomal aberrations both with and without S9 mix. Benzo[h]quinoline was positive without S9 mix, whereas dibenz[c,h]acridine and dibenz[a,j]acridine were only positive with S9 mix. The results suggest that the clastogenic effects of the heavy oil may in part be due to the presence of nitrogen-containing polycyclic hydrocarbons such as aza-arenes.

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A pilot experiment for the micronucleus test. The multi-sampling at multi-dose levels method.

A pilot experiment was undertaken to find the optimal dose range and sampling time in the micronucleus test; 2 animals per group were used. The chemical was injected at 4 different doses, and smear preparations were made from femoral marrow cells at 5 different sampling times for each dose group. The incidence of micronucleated polychromatic erythrocytes was scored on the preparations stained with acridine orange. When the data were arranged two-dimensionally, the optimal dose and sampling time which could be used for a further full-scale test, could be estimated. In addition, sex differences and the effect of multiple treatment can be estimated using this protocol with minor modifications.

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Metabolic fate of N-n-butyl-N-(4-hydroxybutyl)-nitrosamine and its analogues. Selective induction of urinary bladder tumours in the rat.

1. The metabolic fates of N-n-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and N,N-di-n-butylnitrosamine (DBN) were investigated in the rat and other animal species, to elucidate a possible relationship between metabolism and organotropic carcinogenicity to the urinary bladder of these N-nitrosamines. 2. The principal urinary metabolite of BBN as well as of DBN in the rat was N-n-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), which was demonstrated to be the active form of these compounds as bladder carcinogen. The species difference in response to BBN or DBN is discussed on the basis of the urinary excretion rate of BCPN. 3. Metabolism in vivo and carcinogenicity of a number of BBN analogues were investigated in the rat and a general scheme for biotransformation of N-alkyl-N-(omega-hydroxyalkyl)nitrosamines is given. 4. A possible correlation of structure and metabolism with organotropic carcinogenicity of BBN analogues is discussed, with special reference to selective induction of bladder tumours. 5. A clear demonstration of overlapping carcinogenic and mutagenic activities is presented for BBN, DBN and related compounds.

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