5-Azacytidine (5AzC)-induced histopathological changes in the central nervous system of rat fetuses

Ueno, Masaki; Katayama, Kei‐ichi; Yasoshima, Akira; Nakayama, Hiroyuki; Doi, Kunio

doi:10.1078/0940-2993-00239

Cited by 15 publications

(18 citation statements)

References 20 publications

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“…The number of mitotic NPCs reaches the maximum level at 12 hr and returns to the control level at 24 hr after HU administration (Woo et al, 2006). After treatment with 5AzC (Ueno et al, 2002b), the number of mitotic NPCs peaks earlier than the number of apoptotic NPCs at 6 hr, decreases thereafter, reaches the minimum level at 24 hr, and then returns to the control level at 48 hr. At 6 hr, many mitotic cells accumulate in the VZ facing the lateral ventricle, and some of them show pleomorphic mitotic fi gures as observed in tumor cells (Timonen and Therman, 1950;Henderson and Papadimitriou, 1982).…”

Section: Apoptosis and Cell Cycle Arrest In Npcmentioning

confidence: 89%

“…In the VZ of telencephalon, apoptotic cells are mainly observed in the dorsal layer after treatment with ENU (Katayama et al, 2000a) and Ara-C (Yamauchi et al, 2003), in the medial to dorsal layers after treatment with HU (Woo et al, 2003), 6-MP (Kanemitsu et al, 2009c) and VP-16 (Nam et al, 2006a), and in the ventral to medial layers after treatment with 5AzC (Ueno et al, 2002b). As shown in Fig.…”

Section: Apoptosis and Cell Cycle Arrest In Npcmentioning

confidence: 91%

“…As shown in Fig. 2, the number of apoptotic NPCs peaks at 9 to 12 hr and returns to the control level at 48 hr after treatment with ENU (Katayama et al, 2001), HU (Woo et al, 2006), 5AzC (Ueno et al, 2002b), Ara-C (Yamauchi et al, 2004a) and VP-16 (Nam et al, 2006a), while it peaks at 30 hr and returns to the control level at 96 hr after treatment with 6-MP (Kanemitsu et al, 2009c). Following radiation, it peaks at 3 to 5 hr (Borovitskaya et al, 1996).…”

Section: Apoptosis and Cell Cycle Arrest In Npcmentioning

confidence: 99%

“…Moreover, the regulation of this balance also seems to be important during damage due to extrinsic stresses. Cytotoxic stresses induce excessive cell death and suppress cell proliferation in the developing brain (Katayama et al, 2002(Katayama et al, , 2005aUeno et al, 2002aUeno et al, , 2002bYamauchi et al, 2003;Sehata et al, 2004;Semont et al, 2004;Nam et al, 2006aNam et al, , 2006bWoo et al, 2006;Kanemitsu et al, 2009a), and such excess cell death by apoptosis may bring about a lack of cell populations required for later normal histogenesis and organogenesis, resulting in anomalies in the offspring (Inouye and Murakami, 1978;Ferrer et al, 1982Ferrer et al, , 1984Miki et al, 1995;Zhang et al, 1995;Sun et al, 1996Sun et al, , 2001Fushiki et al, 1997;Katayama et al, 2000aKatayama et al, , 2000bKitamura et al, 2001;Woo et al, 2004;Furukawa et al, 2007). Elucidating the mechanisms of how NPCs regulate the cell cycle and apoptosis and respond to exogenous stimuli is important for understanding both normal and abnormal development of the CNS.…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of neurotoxicity induced in the developing brain of mice and rats by DNA-damaging chemicals

Doi

2011

J. Toxicol. Sci.

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-It is not widely known how the developing brain responds to extrinsic damage, although the developing brain is considered to be sensitive to diverse environmental factors including DNA-damaging agents. This paper reviews the mechanisms of neurotoxicity induced in the developing brain of mice and rats by six chemicals (ethylnitrosourea, hydroxyurea, 5-azacytidine, cytosine arabinoside, 6-mercaptopurine and etoposide), which cause DNA damage in different ways, especially from the viewpoints of apoptosis and cell cycle arrest in neural progenitor cells. In addition, this paper also reviews the repair process following damage in the developing brain.

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Section: Apoptosis and Cell Cycle Arrest In Npcmentioning

confidence: 89%

Section: Apoptosis and Cell Cycle Arrest In Npcmentioning

confidence: 91%

Section: Apoptosis and Cell Cycle Arrest In Npcmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mechanisms of neurotoxicity induced in the developing brain of mice and rats by DNA-damaging chemicals

Doi

2011

J. Toxicol. Sci.

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“…Fludarabine, an adenine nucleoside analog, induces cell cycle arrest at G 0 / G 1 (12) and FNC has previously been reported to induce cell cycle arrest in a number of human B-cell lines (4). Numerous nucleoside analogs are used in the treatment of cancer and virus-associated diseases, and abnormal mitosis may always be induced by these analogs (13). FNC may be phosphorylated by cellular kinases and this FNC triphosphate may be then be utilized by DNA replication as a decoy substrate, which once incorporated into a DNA strand causes premature chain termination due to the absence of a 3'-hydroxyl group on the nucleoside sugar.…”

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confidence: 99%

The pyrimidine analog FNC inhibits cell proliferation and viral protein synthesis in HTLV-1-infected cells

Wang

Gao

et al. 2013

Molecular Medicine Reports

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Abstract. Human T-cell leukemia virus type 1 (HTLV-1), the first retrovirus to be identified, is the etiological agent of an aggressive clonal malignancy of mature CD4 + T lymphocytes known as adult T-cell leukemia (ATL). The prognosis of ATL patients remains poor despite the availability of a number of clinical chemotherapy drugs. In addition, HTLV-1-infected and ATL cells possess an intrinsic resistance to anticancer drugs. 2'-Deoxy-2'-β-fluoro-4'-azidocytidine (FNC) is a novel pyrimidine analog that is efficiently phosphorylated by cellular kinases and is a substrate for RNA and DNA polymerases. In the present study, the antiviral potential of FNC was investigated in HTLV-1-infected cell lines. Following FNC treatment, the HTLV-1-infected cells underwent G 1 or S phase cell cycle arrest. FNC was also observed to reduce cell growth of the HTLV-1-infected cell lines in a dose-dependent manner. Notably, FNC was found to efficiently inhibit the expression of the viral proteins, Tax and p19Gag, in a dose-and time-dependent manner. Treatment with FNC and the protein biosynthesis inhibitor, cycloheximide (CHX), accelerated the inhibition of viral protein synthesis in the HTLV-1-infected cells. Collectively, these results demonstrated the efficient antiretroviral effect of FNC in HTLV-1-infected cells and indicate that FNC may be utilized as a valuable therapy in HTLV-1-infected patients and those with ATL. IntroductionHuman T-cell leukemia virus type I (HTLV-1) is an oncogenic retrovirus that causes adult T-cell leukemia/lymphoma (ATL), an aggressive clonal malignancy of mature CD4 + T lymphocytes. ATL has been shown to be the first disease caused by human retroviral infection (1). A number of anticancer drugs have been used in the clinic to treat diseases caused by HTLV-1 infection. However, the prognosis of ATL patients remains poor due to the resistance of ATL cells to anticancer drugs (2). The combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor (PI) or a non-NRTI (NNRTI) is used to control retroviral HIV infection and this type of antiretroviral therapy has been found to significantly reduce mortality rates (3). Since ATL is a malignant disease caused by a retrovirus, it is possible that HTLV-infected and ATL patients may be treated by NRTIs, PIs or NNRTIs or the combination of these inhibitors.At present, 6 NRTIs and 1 nucleotide reverse transcriptase inhibitor are utilized clinically for the treatment of HIV, including 2 thymidine, 2 cytidine, 1 adenine and 2 purine nucleotide analogs (3). Nucleoside analogs may incorporate into nascent viral DNA and cause premature chain termination, leading to an antiviral effect. 2'-Deoxy-2'-β-fluoro-4' -azidocytidine (FNC) is a novel pyrimidine analog that is phosphorylated by cellular kinases and acts as a substrate for RNA and DNA polymerases (4). Previous studies have demonstrated that FNC is a potent inhibitor of hepatitis C virus (HCV) (5) and human and duck hepatitis B virus (HBV) replication (6). In addition, FNC inhibits ...

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Indole-3-acetic acid induces microencephaly in mouse fetuses

Furukawa

Usuda

Abe

et al. 2007

Experimental and Toxicologic Pathology

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5-Azacytidine (5AzC)-induced histopathological changes in the central nervous system of rat fetuses

Cited by 15 publications

References 20 publications

Mechanisms of neurotoxicity induced in the developing brain of mice and rats by DNA-damaging chemicals

Mechanisms of neurotoxicity induced in the developing brain of mice and rats by DNA-damaging chemicals

The pyrimidine analog FNC inhibits cell proliferation and viral protein synthesis in HTLV-1-infected cells

Indole-3-acetic acid induces microencephaly in mouse fetuses

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