Microarray analysis of genes in fetal central nervous system after ethylnitrosourea administration

Katayama, Kei‐ichi; Ueno, Masaki; Yamauchi, Hirofumi; Nakayama, Hiroyuki; Doi, Kunio

doi:10.1002/bdrb.20045

Cited by 6 publications

(8 citation statements)

References 21 publications

(31 reference statements)

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“…, 2002, 2005a). Six hours after ENU treatment (injury phase), genes such as p21 Cip1/WAF1 , bax and mdm2 were up‐regulated in the fetal telencephalon (Katayama et al. , 2005b) explaining the cell cycle arrest that occurred.…”

Section: Resultsmentioning

confidence: 99%

Postnatal exposure to N‐ethyl‐N‐nitrosurea disrupts the subventricular zone in adult rodents

Capilla-González

Gil-Perotín

García-Verdugo

2010

Eur J of Neuroscience

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N-ethyl-N-nitrosurea (ENU), a type of N-nitrous compound (NOC), has been used as inductor for brain tumours due to its mutagenic effect on the rodent embryo. ENU also affected adult neurogenesis when administered during pregnancy. However, no studies have investigated the effect of ENU when exposured during adulthood. For this purpose, three experimental groups of adult mice were injected with ENU at different doses and killed shortly after exposure. When administered in adult mice, ENU did not form brain tumours but led to a disruption of the subventricular zone (SVZ), an adult neurogenic region. Analyses of the samples revealed a reduction in the numbers of neural progenitors compared with control animals, and morphological changes in ependymal cells. A significant decrease in proliferation was tested in vivo with 5-bromo-2-deoxyuridine administration and confirmed in vitro with a neurosphere assay. Cell death, assessed as active-caspase-3 reactivity, was more prominent in treated animals and cell death-related populations increased in parallel. Two additional groups were maintained for 45 and 120 days after five doses of ENU to study the potential regeneration of the SVZ, but only partial recovery was detected. In conclusion, exposure to ENU alters the organization of the SVZ and causes partial exhaustion of the neurogenic niche. The functional repercussion of these changes remains unknown, but exposure to NOCs implies a potential risk that needs further evaluation.

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Section: Resultsmentioning

confidence: 99%

Postnatal exposure to N‐ethyl‐N‐nitrosurea disrupts the subventricular zone in adult rodents

Capilla-González

Gil-Perotín

García-Verdugo

2010

Eur J of Neuroscience

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“…Ln[VEGF] pg/mg total protein. Logarithmic transformation of VEGF concentration values proliferative activity, changing the differentiation of the neuroepithelial progenitors cells from the subventricular plate during the neurogenesis/gliogenesis process (Katayama et al 2005b;Gil-Perotin et al 2006). Recently, using a similar model in rats, the same genetic alterations have been found as in secondary multiform glioblastomas in humans (Kokkinakis et al 2004).…”

Section: Vegf Expressionmentioning

confidence: 95%

VEGF Immunopositivity Related to Malignancy Degree, Proliferative Activity and Angiogenesis in ENU-Induced Gliomas

Bulnes

Lafuente

2007

J Mol Neurosci

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Growth of solid tumors is highly dependent on angiogenesis. During tumor development, neoplastic cells switch to an angiogenic phenotype, playing a significant role in the expression of the vascular endothelial growth factor (VEGF). Seventy-two brain gliomas were induced in Sprague Dawley rats by prenatal exposure to ethylnitrosourea (ENU). Screening and location of tumors was carried out using magnetic resonance imaging (MRI). Conventional histology and immunocytochemistry for antibodies against glial fibrillary acidic protein (GFAP), S-100, NF, oligodendrocyte Ab-2, Ki-67, and VEGF165 were performed. The proliferation index (PI) was calculated from the Ki-67 labeling index, and the concentration of VEGF165 was quantified by enzyme-linked immunosorbent assay (ELISA). In vivo identification of macro- and microtumor appears to be useful to lead morphological and biochemical studies. Histopathology allows us to identify microtumors as classic oligodendrogliomas (CO; mean PI of 6.01 +/- 2.8%) and macrotumors as anaplastic oligodendrogliomas (AO; mean PI of 14.06 +/- 5%). Classic oligodendrogliomas show scarce VEGF165 expression whereas anaplastic ones display VEGF165 protein level 100-fold increased respect to CO. Astrocytes, neoplastic, and endothelial cells show differential immunostaining patterns from the border to the core of neoplasm. Positive structures for VEGF and their distribution vary according to PI increase. Anaplastic gliomas displaying VEGF-positive intratumor capillaries correspond to the highest PI values. To identify the "angiogenic switch," we propose the glioma stage characterized by VEGF immunopositive neoplastic cells inside the tumor and positive endothelial cells surrounding it.

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“…Id proteins work to maintain NPCs in a proliferative state to recover the lost population. Katayama et al (2005b) also reported that the expression of osteopontin was prominently elevated in the recovery phase. Osteopontin is expressed in macrophages of the developing brain and contributes to their migration and phagocytic function (Choi et al, 2004).…”

Section: Repair Process Following Damage In Fetal Brainmentioning

confidence: 93%

“…Further, there has been a recent focus on regenera- tion of neural cells in the adult brain (Magavi et al, 2000;Doetsch, 2003;Picard-Riera et al, 2004). On the other hand, a few researchers have studied the repair period in the developing brain (Oyanagi et al, 1998;Kikuchi-Horie et al, 2004;Vaccarino and Ment, 2004;Katayama et al, 2005b), and, therefore, there is little information about how the repair or recovery process is regulated. Midkine (MK) is a heparin-binding growth factor that occurs as a product of a retinoic acid-inducible gene (Muramatsu, 1994).…”

Section: Repair Process Following Damage In Fetal Brainmentioning

confidence: 99%

“…Using DNA microarray analysis, Katayama et al (2005b) examined the gene expression profiles in the fetal rat CNS at 6 hr (injury phase) and 24 hr (recovery phase) after transplacental administration of ENU on GD13. In the injury phase, the expression of several enzymes required for cholesterol biosynthesis was downregulated and the expression of growth-response protein, which is also known to be involved in cholesterol homeostasis (Janowski, 2002), decreased.…”

Section: Repair Process Following Damage In Fetal Brainmentioning

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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Microarray analysis of genes in fetal central nervous system after ethylnitrosourea administration

Abstract: The present study will provide a better understanding of the mechanisms of development, regeneration and carcinogenesis of the CNS as well as the mechanisms of ENU-induced fetal CNS injury and recovery.

Cited by 6 publications

References 21 publications

Postnatal exposure to N‐ethyl‐N‐nitrosurea disrupts the subventricular zone in adult rodents

Postnatal exposure to N‐ethyl‐N‐nitrosurea disrupts the subventricular zone in adult rodents

VEGF Immunopositivity Related to Malignancy Degree, Proliferative Activity and Angiogenesis in ENU-Induced Gliomas

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

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