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Mechanism of Chromosome aberrations induced by mutagen and carcinogen under the growth stimulation

生长刺激下诱变剂和致癌剂引起染色体畸变的机制

基本信息

批准号：
61570176
负责人：
UEDA Norifumi
金额：
$ 1.22万
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：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570176/
关键词：
Growth factor Chromosome aberrations Sister chromatid exchanges Mutagen and carcinogen 発癌

项目摘要

Acute chromosome-damaging(CA) and chromatid-rearranging(SCE) capacities of various mutagens and carcinogenes such as 7,12-dimethylbenz(a)anthracene(DMBA), 7,8,12-trimethylbenz(a)anthracene(TMBA) and N-nitroso-N-methylurea were sutdied with rat bone marrow cells and fiblasts 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 CA in the anemic rats was 34% and in the polycythemic rats, it was 18%(normal rats 23%). However, the incidence of CA in polycythemic rats inoculated with 6 Units of erythropietin at the time of DMBA injection was 32%. Therefore, the percentage of metaphase cells with CA induced by DMBA was enhanced by anemia and suppressed by polycythemia. The low incidence of CA in polycythemic rats was reversed by 6 units of sheep erythropoietion injected at the time of DMBA treatment. CA were distributed nonrandomly in chromosomes 1 and 2. One region, the 40% region from the centromere, of the long arm of chromosome 1, and two regions, 30 and 55% from the centromere, of chromosome 2 were extremely susceptible to DMBA in the normal hematopoietic state. Also, the enhancing effect of erythropoietin on DMBA-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 fibroblasts, the frequency of SCE induced by NMU was enhanced with addition of fibroblastic growth factor in cultured medium in vitro.In the TMBA-induced leukemogenesis, sex hormone may somehow be associated with carcinogenesis.The above enhanced susceptibilityofcertainchromosomal regions to chemical carcinogens under growth stimuli is important in respect to the fact that growth stimuli given before carcinogen treatment enhance carcinogenesis in organs.

用大鼠骨髓细胞和成纤维细胞研究了7，12-二甲基苯并(A)菲(DMBA)、7，8，12-三甲基苯并(A)菲(TMBA)和N-亚硝基-N-甲基脲(TMBA)等多种致突变剂和致癌物的急性染色体损伤(CA)和染色单体重排(SCE)能力。检测上述致癌物在不同刺激条件下的染色体畸变率(CA)和姐妹染色单体互换(SCE)率。贫血大鼠CA发生率为34%，红细胞增多症大鼠为18%，正常大鼠为23%。而注射DMBA时接种6单位红细胞增多症大鼠的CA发生率为32%。因此，DMBA诱导的CA中期细胞比例因贫血而升高，而因红细胞增多症而受到抑制。在DMBA治疗的同时注射6个单位的绵羊红细胞可逆转红细胞增多症大鼠CA的低发生率。CA非随机分布于第1、2号染色体。在正常造血状态下，第1号染色体着丝粒的40%区域和第2染色体着丝粒的30%和55%的两个区域对DMBA极敏感。此外，促红细胞生成素对DMBA诱导的CA的增强作用被认为是染色体区域特有的。在贫血条件下，姐妹染色单体交换频率升高，在红细胞增多症条件下，姐妹染色单体交换频率降低。在成纤维细胞中，NMU诱导的姐妹染色单体交换频率随着培养上清液中成纤维细胞生长因子的加入而增加。在TMBA诱发的白血病中，性激素可能在某种程度上与致癌有关。在生长刺激下，某些染色体区域对化学致癌物的敏感性增加，这是在致癌物治疗前给予生长刺激促进器官致癌的重要因素。