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Evaluation of sister chromatid exchange as an indicator of sensitivity toN‐ethyl‐N‐nitrosourea‐induced carcinogenesis in rats

机译:评估姐妹染色单体交换作为对N-乙基-N-亚硝基脲诱导的大鼠癌变敏感性的指标

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AbstractSister chromatid exchange (SCE) frequencies in peripheral lymphocytes are a frequently used endpoint to indicate exposures to genotoxins in groups of humans. The aim of this study was to ascertain, in an experimental design, whether or not SCE rates have any association with the risk of cancer at the individual level in rats exposed to a known carcinogen. Individual SCE rates were determined in three consecutive analyses in cultured blood lymphocytes of 50 adult male Wistar rats. Analyses were done before as well as 24 hr and 7 days after a single intraperitoneal administration of 0, 25, 50, or 75 mg/kg ofN‐ethyl‐N‐nitrosourea (ENU). The animals were followed until death; also, the relationship between SCEs and carcinogenic outcome, i.e., the presence or absence of tumors, and their latency period were examined. ENU significantly decreased the life expectancy of the rats. The tumor types most clearly associated with ENU treatment were various gliomas and thyroid‐gland and testicular tumors. ENU induced a moderate (maximally 1.6‐fold) increase in the mean frequency of SCEs/cell at both sampling times after treatment. The effect was somewhat more pronounced 1 day rather than 1 week after treatment. The mean SCE rates in rats with ENU‐specific cancers or in animals with early or multiple tumors did not differ from those in animals that survived no less than 65 weeks or longer without developing tumors. In ENU‐treated animals with tumors, no relationship was found between the mean SCE rate and survival time. It is concluded that in outbred Wistar rats the SCE response in cultured lymphocytes does not indicate individual susceptibility to the carcinogenic action of ENU. On a group basis, however, animals with high SCE rates were shown to have increased r
机译:摘要外周淋巴细胞中的姐妹染色单体交换(SCE)频率是指示人类群体中基因毒素暴露的常用终点。本研究的目的是在实验设计中确定 SCE 率是否与暴露于已知致癌物的大鼠个体水平的癌症风险有任何关联。在 50 只成年雄性 Wistar 大鼠的培养血淋巴细胞中连续三次分析中测定了个体 SCE 率。在单次腹膜内给药 0、25、50 或 75 mg/kg N-乙基-N-亚硝基脲 (ENU) 之前以及 24 小时和 7 天进行分析。这些动物被跟踪直到死亡;此外,还研究了 SCE 与致癌结果之间的关系,即肿瘤的存在与否,以及它们的潜伏期。ENU显著降低了大鼠的预期寿命。与ENU治疗最明显的肿瘤类型是各种神经胶质瘤以及甲状腺和睾丸肿瘤。ENU诱导治疗后两个采样时间SCEs/细胞的平均频率适度(最大1.6倍)增加。治疗后 1 天而不是 1 周的效果更明显。患有ENU特异性癌症的大鼠或患有早期或多发肿瘤的动物的平均SCE率与存活不少于65周或更长时间而未发生肿瘤的动物的平均SCE率没有差异。在ENU治疗的肿瘤动物中,没有发现平均SCE率与生存时间之间的关系。得出的结论是,在近交系Wistar大鼠中,培养淋巴细胞中的SCE反应并不表明个体对ENU致癌作用的易感性。然而,在群体基础上,具有高 SCE 率的动物被证明具有增加的 r

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