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首页> 外文期刊>Toxicologic pathology >Induction of pancreatic islet cell tumors in rats by repeated intravenous administration of 4-hydroxyaminoquinoline 1-oxide.
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Induction of pancreatic islet cell tumors in rats by repeated intravenous administration of 4-hydroxyaminoquinoline 1-oxide.

机译：通过反复静脉内注射4-羟基氨基喹啉1-氧化物诱导大鼠胰岛细胞瘤。

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The inducibility of pancreatic islet cell tumors by administration of 4-hydroxyaminoquinoline 1-oxide (4HAQO) was investigated in male 6-week-old Sprague-Dawley rats. Rats were given 4HAQO intravenously at a weekly dose of 5 mg/kg 4 times (group 1) or a single dose of 10 mg/kg (group 2). Control rats received the vehicle alone (group 3). Fifty-six weeks after the first 4HAQO administration, all surviving animals were killed and the pancreas was examined histopathologically, immunohistochemically and ultrastructurally. The incidences and multiplicities of islet cell tumors in groups 1, 2, and 3 were 52.3% (p < 0.05 vs group 2, p < 0.01 vs group 3), 19.2% and 0%, and 0.70/animal (p < 0.05 vs group 2, p < 0.01 vs group 3), 0.23 and 0, respectively. Islet cell carcinomas were induced only in group 1, accounting for 6/44 (26%) tumors. Islet cell hyperplasias were found in 61.4% (p < 0.05 vs group 3), 42.3% and 10.0% of groups 1, 2, and 3, with multiplicities of 0.95 (p < 0.05 vs groups 2 and 3), 0.54 and 0.20, respectively. As compared with normal islets from control subjects, islet cell tumors showed an increase in the number of insulin positive cells associated with cytological features indicative of enhanced insulin synthesis and secretion, and a decrease in the number of glucagon positive cells without ultrastructural signs of modified secretory activity. Thus our results indicate that repeated intravenous administration of 4HAQO to rats is useful for the induction of islet cell tumors at high incidence.
机译：在雄性6周大的Sprague-Dawley大鼠中研究了通过使用4-羟基氨基喹啉1氧化物（4HAQO）诱导的胰岛细胞肿瘤的诱导性。每周给大鼠静脉注射4HAQO，剂量为4次每周5 mg / kg（第1组）或单次剂量为10mg / kg（第2组）。对照大鼠仅接受媒介物（第3组）。首次施用4HAQO后56周，杀死了所有存活的动物，并进行了组织病理学，免疫组织化学和超微结构检查。第1、2和3组胰岛细胞瘤的发生率和多重性分别为52.3％（p <0.05 vs第2组，p <0.01 vs第3组），19.2％和0％，以及0.70 /动物（p <0.05 vs.第2组，相对于第3组，p <0.01，分别为0.23和0。仅在第1组中诱发胰岛细胞癌，占6/44（26％）肿瘤。胰岛细胞增生在第1、2和3组中分别占61.4％（p <0.05，与第3组相比），42.3％和10.0％，分别为0.95（p <0.05，与第2和3组相比），0.54和0.20，分别。与正常人的胰岛细胞相比，胰岛细胞瘤的胰岛素阳性细胞数量增加，这些细胞学特征与指示胰岛素合成和分泌增强的细胞学特征有关，胰高血糖素阳性细胞数量减少，而没有超微结构的分泌改变迹象活动。因此，我们的结果表明，向大鼠重复静脉内施用4HAQO有助于高发病率诱导胰岛细胞肿瘤。

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