Cytogenetic studies on causes of congenital heart diseases - Factors associated with an increase in sister chromatid exchanges -

先天性心脏病病因的细胞遗传学研究 - 与姐妹染色单体交换增加相关的因素 -

• 批准号: 60570252
• 负责人: KAGAMIMORI Sadanobu
• 金额: $ 0.32万
• 依托单位: Toyama Medical and Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60570252/
• 关键词: Congenital heart disease; Peripheral blood lymphocyte; Sister chromatid exchanges; Micronucleus; Fertilysine; Nydran; Pregnant exposure; マウス胎仔肝

It has been well known that the frequency of sister chromatid exchanges (SCE) and micronuclei (MN) are indirect, but sensitive indicators of chromosome damages. In the present study, cytogenetic investigations on genetic-environmental interaction in the etiology of congenital heart disease (CHD) were performed by means of the SCE and MN test. The frequencies of SCE and MN in peripheral blood lymphocytes of CHD children were significantly higher compared with those of the reference group. The frequencies of CHD children were not dependent on the digitalis treatment and types of the anomalies. Furthermore, the frequencies of the patient's mothers were also significantly higher compared with those of the reference females. In vitro exposure experiment, agents associated with CHD development such as fertilysine, nydran, LiCl, Trimethadione and Diethystilbesterol could induce an increase in SCE and MN frequencies in peripheral blood lymphocytes.In animal model for pregnant exposure, fertilysine administrated on day 14 gestation could induce a statistically significant increase in the drequency of polychromatic erythrocytes with MN in the fetal liver. On the otherhand corticosterone, a reference agent, could not affect the frequency.The present study points out that the SCE and MN test are useful tools for the cytogenetic investigations of the etiology of CHD.

姐妹染色单体交换频率（SCE）和微核频率（MN）是染色体损伤的间接但敏感的指标。在本研究中，通过SCE和MN试验对先天性心脏病（CHD）病因中的遗传-环境相互作用进行了细胞遗传学研究。冠心病患儿外周血淋巴细胞中SCE和MN的频率明显高于对照组。冠心病患儿的发病频率与洋地黄治疗和异常类型无关。此外，患者母亲的频率也明显高于参考女性。在体外暴露实验中，与冠心病发生相关的药物如肥赖氨酸、尼德兰、LiCl、甲美二酮和己烯雌酚可诱导外周血淋巴细胞SCE和MN频率升高。在妊娠暴露动物模型中，妊娠第14天给药肥赖氨酸可诱导胎儿肝脏中MN多染红细胞的频率有统计学意义的增加。另一方面，皮质酮作为对照剂，不影响频率。本研究指出，SCE和MN试验是冠心病病因的细胞遗传学研究的有用工具。

项目成果

藤田孝子,成瀬優知,鏡森定信: 日本公衆衛生雑誌. 33. 165-172 (1986)

Takako Fujita、Yuchi Naruse、Sadanobu Kagamori：日本公共卫生杂志 33. 165-172 (1986)。

T. Fujita, Y. Naruse, S. Kagamimori and M. Watanabe: "A consideration of the cytogenetics associated with drug-induced external malformation - A comparative study on fertilysine and corticosterone -" Japanese Journal of Public Health. 33. 165-172 (1986)

T. Fujita、Y. Naruse、S. Kagamimori 和 M. Watanabe：“考虑与药物引起的外部畸形相关的细胞遗传学 - 肥赖氨酸和皮质酮的比较研究 -”日本公共卫生杂志。

T. Makino, S. Kagamimori, M. Watanabe, T.Iwa, and A. Okada: "Sister Chromatid Exchange in Children with congenital heart disease." Mutation Research.

T. Makino、S. Kagamimori、M. Watanabe、T.Iwa 和 A. Okada：“先天性心脏病儿童中的姐妹染色单体交换”。

Makino,T;,Kagamimori,S;,Watanabe,M;,Iwa,T.Okada,A.: Mutation Research(in application).

Makino,T;,Kagamimori,S;,Watanabe,M;,Iwa,T.Okada,A.：突变研究（应用中）。