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来自美国国家毒理学计划致癌生物测定项目短期、慢性前期和慢性研究的B6C3F(1)小鼠外周血中的微核红细胞频率。

Micronucleated erythrocyte frequency in peripheral blood of B6C3F(1) mice from short-term, prechronic, and chronic studies of the NTP carcinogenesis bioassay program.

作者信息

Witt K L, Knapton A, Wehr C M, Hook G J, Mirsalis J, Shelby M D, MacGregor J T

机构信息

ILS, Inc., Research Triangle Park, North Carolina 27709, USA.

出版信息

Environ Mol Mutagen. 2000;36(3):163-94.

Abstract

The mouse peripheral blood micronucleus (MN) test was performed on samples collected from 20 short-term, 67 subchronic, and 5 chronic toxicity and carcinogenicity studies conducted by the National Toxicology Program (NTP). Data are presented for studies not previously published. Aspects of protocol that distinguish this test from conventional short-term bone marrow MN tests are duration of exposure, and absence of repeat tests and concurrent positive controls. Furthermore, in contrast to short-term bone marrow MN tests where scoring is limited to polychromatic erythrocytes (PCE), longer term studies using peripheral blood may evaluate MN in both, or either, the normochromatic (NCE) or PCE populations. The incidence of MN-PCE provides an index of damage induced within 72 hr of sampling, whereas the incidence of MN in the NCE population at steady state provides an index of average damage during the 30-day period preceding sampling. The mouse peripheral blood MN test has been proposed as a useful adjunct to rodent toxicity tests and has been effectively incorporated as a routine part of overall toxicity testing by the NTP. Data derived from peripheral blood MN analyses of dosed animals provide a useful indication of the in vivo potential for induced genetic damage and supply an important piece of evidence to be considered in the overall assessment of toxicity and health risk of a particular chemical. Although results indicate that the test has low sensitivity for prediction of carcinogenicity, a convincingly positive result in this assay appears to be highly predictive of rodent carcinogenicity.

摘要

对从美国国家毒理学计划(NTP)开展的20项短期、67项亚慢性以及5项慢性毒性和致癌性研究中收集的样本进行了小鼠外周血微核(MN)试验。本文呈现了此前未发表研究的数据。该试验与传统短期骨髓MN试验的不同之处在于暴露持续时间、无重复试验以及无同期阳性对照。此外,与短期骨髓MN试验不同,短期骨髓MN试验的评分仅限于多染性红细胞(PCE),而使用外周血的长期研究可评估正染性红细胞(NCE)群体或PCE群体中的微核,或两者皆评估。MN-PCE的发生率提供了采样后72小时内诱导损伤的指标,而稳态下NCE群体中MN的发生率提供了采样前30天内平均损伤的指标。小鼠外周血MN试验已被提议作为啮齿动物毒性试验的有用辅助手段,并已被NTP有效地纳入整体毒性试验的常规部分。给药动物外周血MN分析得出的数据为诱导遗传损伤的体内潜力提供了有用的指示,并为特定化学品毒性和健康风险的整体评估提供了一项重要证据。尽管结果表明该试验对致癌性预测的敏感性较低,但该试验中令人信服的阳性结果似乎对啮齿动物致癌性具有高度预测性。

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