[PMID]: | 26763396 |
[Au] Autor: | Kimura M; Mizukami S; Watanabe Y; Hasegawa-Baba Y; Onda N; Yoshida T; Shibutani M |
[Ad] Endereço: | Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology. |
[Ti] Título: | Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens. |
[So] Source: | J Toxicol Sci;41(1):91-104, 2016 Feb. |
[Is] ISSN: | 1880-3989 |
[Cp] País de publicação: | Japan |
[La] Idioma: | eng |
[Ab] Resumo: | We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration. |
[Mh] Termos MeSH primário: |
Antraquinonas/administração & dosagem Antraquinonas/toxicidade Rim/citologia Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos Nitrofurantoína/administração & dosagem Nitrofurantoína/toxicidade Propano/análogos & derivados
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[Mh] Termos MeSH secundário: |
Animais Peso Corporal/efeitos dos fármacos Carboxina/administração & dosagem Carboxina/toxicidade Proliferação Celular/efeitos dos fármacos Cloridrinas/administração & dosagem Cloridrinas/toxicidade Histonas/metabolismo Rim/efeitos dos fármacos Masculino Tamanho do Órgão/efeitos dos fármacos Propano/administração & dosagem Propano/toxicidade Ratos Endogâmicos F344 Fatores de Tempo Triantereno/administração & dosagem Triantereno/toxicidade Ubiquitinas/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Anthraquinones); 0 (Chlorohydrins); 0 (Histones); 0 (UBD protein, human); 0 (Ubiquitins); 3MJ7QCK0Z0 (1,2,3-trichloropropane); 5A8K850HDE (Carboxin); 927AH8112L (Nitrofurantoin); RF75O3IKOZ (1-amino-2,4-dibromoanthraquinone); T75W9911L6 (Propane); WS821Z52LQ (Triamterene); ZL0FUS96WW (1-chloro-2-propanol) |
[Em] Mês de entrada: | 1609 |
[Cu] Atualização por classe: | 160114 |
[Lr] Data última revisão:
| 160114 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 160115 |
[St] Status: | MEDLINE |
[do] DOI: | 10.2131/jts.41.91 |
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