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Influence of cell-proliferating stimuli on carcinogen-induced chromosome aberrations and sister chromitid exchanges

细胞增殖刺激对致癌物诱导的染色体畸变和姐妹染色单体交换的影响

基本信息

批准号：
04670212
负责人：
UEDA Norifumi
金额：
$ 1.15万
依托单位：
Ehime 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：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

Acute chromosome-damaging and chromatid-rearranging capacities of various mutagens and carcinogenes such as 7,12-dimethylbenz(a)anthracene(DMBA), and N-nitroso-N-methylurea(NMU) were studied with rat bone marrow cells, liver cells and fibroblasts in vivo and in vitro. The frequency of chromosome aberrations(CA) and sister chromatid exchange(SCE) after administration of above-mentioned carcinogens was tested under various stimuli. The incidence of DMBA-and NMU-induced CA in the anemic rats was 45% and 56%, and in the polycythemic rats, it was 17% and 24%(normal rats 28-33%). However, the incidence of CA in polycythemic rats inoculated with 6 Units of erythropietin at the time of DMBA injection was 41% and 47%. In the other words, the percentage of metaphase cells with CA induced by DMBA was enhanced by anemia andsuppressed by polycythemia. The low incidence of CA in polycythemic rats was re-versed by 6 units of sheep erythropoietin injected at the time of DMBA and NMU treatment. CA were distributed nonrandomly in chromosomes 1 and 2. One region, the 40% region from the centromere(1q31), of the long arm of chromosome 1, and three regions, 30, 55 and 80% from the centromere(2q21, 2q25, 2q41), of chromosome 2 were extremely susceptible to DMBA and NMU in the normal hematopietic state. Also, the enhancing effect of erythropoietin on DMBA- and NMU- induced CA was considered specific with respect to chromosomal regions. The frequency of SCE was increased under the condition of anemia and that of SCE was decreased under the condition of polycythemia. In liver cell obtained hepatectomized rats, the frequency of SCE induced by DMBA was enhanced with addition of the liver cell growth factor in vivo(from 13.5% to 28.3%). In fibroblasts, the frequency of SCE induced by NMU was enhanced in the ratio of 1.5 times with addition of thefibroblastic growth factor in cultured medium in vitro.

用大鼠骨髓细胞、肝细胞和成纤维细胞研究了7，12-二甲基苯蒽（DMBA）和N-亚硝基-N-甲基脲（NMU）等致突变剂和致癌剂的急性染色体损伤和染色单体重排能力。在各种刺激条件下，检测了上述致癌物对小鼠染色体畸变（CA）和姐妹染色单体交换（SCE）的影响。DMBA和NMU诱发的CA在贫血大鼠中的发生率分别为45%和56%，在红细胞增多症大鼠中分别为17%和24%（正常大鼠为28-33%）。而在注射DMBA时接种6单位促红细胞生成素的红细胞增多症大鼠中，CA的发生率为41%和47%。也就是说，DMBA诱导的CA的中期细胞百分比在贫血时增加，而在红细胞增多时减少。在DMBA和NMU治疗的同时注射6个单位的绵羊促红细胞生成素可逆转红细胞增多症大鼠CA的低发病率。CA非随机分布于1号和2号染色体。在正常造血状态下，1号染色体长臂40%区域（1 q31）和2号染色体长臂30%、55%和80%区域（2 q21、2 q25、2 q41）对DMBA和NMU高度敏感。此外，促红细胞生成素对DMBA和NMU诱导的CA的增强作用被认为是特定于染色体区域的。贫血时SCE频率增高，红细胞增多时SCE频率降低。在肝切除大鼠肝细胞中，加入肝细胞生长因子后，DMBA诱发的SCE频率增加（从13.5%增加到28.3%）。在成纤维细胞中，加入成纤维细胞生长因子后，NMU诱导的SCE频率提高了1.5倍。