Aitio A, Cabral J R, Camus A M, Galendo D, Bartsch H, Aitio M L, Norppa H, Salomaa S, Sorsa M, Husgafvel-Pursiainen K
International Agency for Research on Cancer, Lyon, France.
Teratog Carcinog Mutagen. 1988;8(5):273-86. doi: 10.1002/tcm.1770080504.
Sister 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 of N-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 risk of cancer.
外周淋巴细胞中的姐妹染色单体交换（SCE）频率是用于指示人类群体中基因毒素暴露情况的常用指标。本研究的目的是在一项实验设计中确定，在暴露于已知致癌物的大鼠个体水平上，SCE率是否与癌症风险存在任何关联。在50只成年雄性Wistar大鼠的培养血淋巴细胞中进行了连续三次分析，以确定个体SCE率。在单次腹腔注射0、25、50或75mg/kg的N-乙基-N-亚硝基脲（ENU）之前以及注射后24小时和7天进行分析。对动物进行跟踪直至死亡；此外，还检查了SCE与致癌结果之间的关系，即肿瘤的有无及其潜伏期。ENU显著降低了大鼠的预期寿命。与ENU治疗最明显相关的肿瘤类型是各种胶质瘤、甲状腺肿瘤和睾丸肿瘤。ENU在治疗后的两个采样时间点均使每个细胞的SCE平均频率适度增加（最大为1.6倍）。治疗后1天的效果比1周时更为明显。患有ENU特异性癌症的大鼠或患有早期或多发性肿瘤的动物的平均SCE率与存活不少于65周或更长时间且未发生肿瘤的动物的平均SCE率没有差异。在接受ENU治疗并患有肿瘤的动物中，未发现平均SCE率与存活时间之间的关系。结论是，在远交系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，从群体角度来看，SCE率高的动物患癌症的风险增加。
