Incubation of mouse thymocytes with arabinosylcytosine or 5-azacytidine induced dose-dependent internucleosomal DNA cleavage followed by cell death. This process was RNA and protein synthesis-dependent, since DNA fragmentation and cell death was inhibited by actinomycin D and cycloheximide. The results suggest that the cytidine analogs induce apoptosis, a programmed cell death, in thymocytes. The DNA cleavage induced by arabinosylcytosine and 5-azacytidine was inhibited by deoxycytidine and cytidine, respectively, suggesting that phosphorylation of these antimetabolites is required to induce DNA cleavage. DNA fragmentation was unaffected by the addition of aphidicolin or 3-aminobenzamide, indicating that DNA cleavage is not due to the inhibition of DNA synthesis or repair. Other antimetabolites including methotrexate, fluoropyrimidines and thiopurines failed to induce DNA fragmentation. Arabinosylguanine induced DNA fragmentation similar to that produced by the cytidine analogs, suggesting similarity to the selective sensitivity of T lymphocytes to deoxyguanosine toxicity. The precise mechanism by which DNA cleavage is induced remains unclear, but the present study shows that certain antimetabolites act on cells not only by inhibiting proliferation, but by inducing apoptosis with internucleosomal DNA fragmentation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

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1-beta-D-arabinosylcytosine and 5-azacytidine induce internucleosomal DNA fragmentation and cell death in thymocytes.

Incubation of mouse thymocytes with arabinosylcytosine or 5-azacytidine induced dose-dependent internucleosomal DNA cleavage followed by cell death. This process was RNA- and protein synthesis-dependent, since DNA fragmentation and cell death was inhibited by actinomycin D and cycloheximide. The results suggest that the cytidine analogs induce apoptosis, a programmed cell death, in thymocytes. The DNA cleavage induced by arabinosylcytosine and 5-azacytidine was inhibited by deoxycytidine and cytidine, respectively, suggesting that phosphorylation of these antimetabolites is required to induce DNA cleavage. DNA fragmentation was unaffected by the addition of aphidicolin or 3-aminobenzamide, indicating that DNA cleavage is not due to the inhibition of DNA synthesis or repair. Other antimetabolites, including methotrexate, fluoropyrimidines and thiopurines, failed to induce DNA fragmentation. Arabinosylguanine induced DNA fragmentation similar to that produced by the cytidine analogs, suggesting similarity to the selective sensitivity of T lymphocytes to deoxyguanosine toxicity. The precise mechanism by which DNA cleavage is induced remains unclear, but the present study shows that certain antimetabolites act on cells not only by inhibiting proliferation, but by inducing apoptosis with internucleosomal DNA fragmentation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMedDate not supplied

Synergic stimulation of arabinosylcytosine induced apoptosis in mouse thymocytes by cyclic AMP.

Previous studies demonstrated that arabinosylcytosine (ara-C) induced internucleosomal DNA fragmentation and cell death in mouse thymocytes and that those were inhibited by 1-(5-iso-quinoline-sulfonyl)-2-methylpiperazine hydrochloride, an inhibitor of protein kinases. In the present study, we examined the relationship between the DNA fragmentation induced by ara-C and that by agents which activate intracellular signaling and induce apoptosis in mouse thymocytes. 12-O-tetradecanoyl 13-acetate, a phorbol ester capable of activating protein kinase C or A23187, a calcium ionophore, had no effect on ara-C induced DNA fragmentation. However, ara-C induced DNA fragmentation was synergistically enhanced by cAMP and cAMP receptor agonists. Ara-C inhibited the incorporation of choline into the acid soluble and lipid fractions, and cAMP enhanced this inhibition, suggesting that ara-C metabolites interfere with membrane phospholipid metabolism, partly evoking a certain cellular signaling for apoptosis and interacting with cAMP-evoked signaling.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMedDate not supplied

Experimental gingivitis: development of a new strain of plaque-susceptible rat.

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Systemic effects of the occlusal destruction in guinea pigs.

Although there is an increasing amount of information pertaining to the systemic effects of malocclusion, its mechanisms still remain unclear in many ways. This study was conducted to find out the systemic effects of the occlusal destruction in guinea pigs. The animals showed an abnormality in posture and a reversal of the T wave in electrocardiogram (ECG) about 6 days after the grinding of all molar teeth. All the animals died about 7 days after the occlusal destruction. We established the optimal condition of occlusal destruction for the induction of the above symptoms in guinea pigs: at least 6 molars, both side premolar, 1st and 2nd molar of upper jaw, because of the ease for repair. The following results were obtained: 1. The experimental group died about 5 days earlier than the fasting group. 2. The animals could not hold their head positions and dropped the head to the earth. 3. The animals died about 12 hours after the onset of postural abnormality. 4. Ninety percent of the animals with postural abnormalities showed T wave inversion on ECG. 5. None of the above symptoms occurred with bite rising. These results indicate that occlusal destruction affects head position, preventing the animals to hold their head positions and causing the head to drop to the ground. Occlusal destruction may also cause abnormality of the masticatory muscles, which control posture and modulate cardiac function via the trigeminal system. This experimental model is suitable for the analysis of the systemic effects of occlusal destruction.

Animals↗

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Characterization of Newcastle disease viruses isolated from field cases in Japan.

Seven Newcastle disease viruses isolated in Japan from 1930 to 1984 were cloned on chicken embryo fibroblasts (CEFs) and characterized biologically. All seven produced two or more types of plaques on CEFs. The plaques were classified into four types. Plaque cloning was carried out five times, and 22 cloned viruses were established. The biological characters of the cloned viruses suggested that the strains contain different clones and that their clones are different even among close cases, such as G strain and H strain.

Animals↗