Association of chromosomal alterations with arsenite-induced tumorigenicity of human HaCaT keratinocytes in nude mice.
Association of chromosomal alterations with arsenite-induced tumorigenicity of human HaCaT keratinocytes in nude mice.
复制标题
染色体改变与砷诱导的裸鼠角质形成细胞的肿瘤性的染色体改变的关联。
DOI：
10.1289/ehp.7224
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发表时间：
2004-12
影响因子：
10.4
通讯作者：
Lee TC
中科院分区：
文献类型：
--
作者：
Chien CW;Chiang MC;Ho IC;Lee TC
无机砷是一种有据可查的人类致癌物。长期低剂量接触无机砷与多种癌症的发病率增加有关，包括皮肤癌、肺癌、膀胱癌和肝癌。由于遗传改变经常发生在癌症的发展过程中，本研究的目的是探讨人类HaCaT细胞慢性暴露于砷诱导的遗传改变类型。在0.5或1 μM浓度的无机三价亚砷酸盐存在下传代20次后，HaCaT细胞具有更高的细胞内谷胱甘肽水平，对亚砷酸盐更具抗性，并显示微核频率增加。此外，先前非致瘤性HaCaT细胞变成致瘤性，如通过皮下注射到Balb/c裸鼠中所示。通过将暴露于亚砷酸盐的HaCaT细胞注射到裸鼠中形成的肿瘤衍生的细胞系表达了比亲本HaCaT细胞更高水平的角蛋白6（角质形成细胞的增殖标志物），而角蛋白5、8和10的表达显著降低。比较基因组杂交显示，来自这些肿瘤的11个细胞系中的染色体改变;所有11个细胞系显示染色体9 q的显著丢失，7个细胞系显示染色体4 q的显著增加。目前的研究结果表明，长期暴露于低剂量的亚砷酸盐转化nontumorigenic人角质形成细胞的细胞，在裸鼠中的致瘤性和染色体的改变中观察到的所有细胞系建立从肿瘤。
Inorganic arsenic is a well-documented human carcinogen. Chronic low-dose exposure to inorganic arsenic is associated with an increased incidence of a variety of cancers, including skin, lung, bladder, and liver cancer. Because genetic alterations often occur during cancer development, the objective of this study was to explore what types of genetic alterations were induced by chronic exposure of human HaCaT cells to arsenic. After 20 passages in the presence of inorganic trivalent arsenite at concentrations of 0.5 or 1 μM, HaCaT cells had higher intracellular levels of glutathione, became more resistance to arsenite, and showed an increased frequency of micronuclei. Furthermore, the previously nontumorigenic HaCaT cells became tumorigenic, as shown by subcutaneous injection into Balb/c nude mice. Cell lines derived from the tumors formed by injection of arsenite-exposed HaCaT cells into nude mice expressed higher levels of keratin 6, a proliferation marker of keratinocytes, than did parental HaCaT cells, whereas the expression of keratins 5, 8, and 10 was significantly decreased. Comparative genomic hybridization demonstrated chromosomal alterations in the 11 cell lines derived from these tumors; all 11 showed significant loss of chromosome 9q, and seven showed significant gain of chromosome 4q. The present results show that long-term exposure to low doses of arsenite transformed nontumorigenic human keratinocytes to cells that were tumorigenic in nude mice and that chromosomal alterations were observed in all cell lines established from the tumors.
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影响因子：
10.4
作者：
Centeno JA;Mullick FG;Martinez L;Page NP;Gibb H;Longfellow D;Thompson C;Ladich ER
通讯作者：
Ladich ER
影响因子：
8.3
作者：
Calderón, J;Navarro, ME;Díaz-Barriga, F
通讯作者：
Díaz-Barriga, F
影响因子：
4.4
作者：
Habuchi, T;Luscombe, N;Knowles, MA
通讯作者：
Knowles, MA
影响因子：
2.7
作者：
FENECH, M;MORLEY, AA
通讯作者：
MORLEY, AA
影响因子：
8.3
作者：
CHEN, CJ;HSUEH, YM;TAI, TY
通讯作者：
TAI, TY