Enhanced sensitivity of the C3H/10T1/2 cell transformation system to alkylating and chemotherapeutic agents by treatment with 12-O-tetradecanoylphorbol-13-acetate.

Enhanced sensitivity of the C3H/10T1/2 cell transformation system to alkylating and chemotherapeutic agents by treatment with 12-O-tetradecanoylphorbol-13-acetate.
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通过 12-O-tetradecanoylphorbol-13-acetate 处理,增强 C3H/10T1/2 细胞转化系统对烷化剂和化疗剂的敏感性。

DOI:
10.1002/em.2860060110
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发表时间:
1984
期刊:
Environmental mutagenesis
影响因子:
--
通讯作者:
C. Boreiko
C. Boreiko
中科院分区:
--
文献类型:
--
作者:
J. H. Frazelle;D. Abernethy;C. Boreiko

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C3 H/10 T1/2细胞转化系统对许多已知致癌物的反应失败,限制了其在致癌物质检测和研究中的应用。然而,最近的研究发现,一些致癌物质在这些细胞中起着转化过程的起始剂的作用。用这样的试剂处理通常不足以转化C3 H/10 T12细胞的低密度异步培养物,但如果随后将这样的培养物暴露于有效的肿瘤促进剂12-O-十四烷酰基佛波醇-13-乙酸酯(TPA),则会发生形态转化。在本研究中,在用各种化学试剂处理的培养物中检查了TPA增强转化的能力。化学处理后加入TPA增强了甲磺酸甲酯、甲磺酸乙酯、N-甲基-N '-硝基-N-亚硝基胍、N-亚硝基甲基脲、N-亚硝基乙基脲、丝裂霉素C、5-氟脱氧尿苷和5-氮杂胞苷对这些细胞的转化。在TPA存在或不存在的情况下,用氨甲喋呤或苯并(e)芘治疗没有产生显著数量的病灶。TPA抑制转化高浓度的3-甲基胆蒽和苯并(a)芘。因此,许多致癌物作为这些细胞的起始剂,TPA的存在可以显着增加这种细胞转化系统的敏感性。
The failure of the C3H/10T1/2 cell transformation system to respond to numerous known carcinogens has limited its applications for the detection and study of cancer-causing substances. Recent studies have found, however, that some carcinogens function as initiating agents for the process of transformation in these cells. Treatment with such agents is generally not sufficient to transform low-density asynchronous cultures of C3H/10T1/2 cells, but morphologic transformation will occur if such cultures are subsequently exposed to the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). In the present study, the ability of TPA to enhance transformation was examined in cultures treated with a variety of chemical agents. The addition of TPA after chemical treatment enhanced the transformation of these cells by methylmethanesulfonate, ethylmethanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, N-nitrosomethylurea, N-nitrosoethylurea, mitomycin C, 5-fluorodeoxyuridine, and 5-azacytidine. Treatment with amethopterin or benzo(e)pyrene did not produce significant numbers of foci in the presence or absence of TPA. TPA inhibited transformation by high concentrations of 3-methylcholanthrene and benzo(a)pyrene. Thus, numerous carcinogens function as initiating agents for these cells and the presence of TPA can dramatically increase the sensitivity of this cell transformation system.
用 N-甲基-N-硝基-N-亚硝基胍处理的 10T1/2 细胞中的循环相关毒性和转化。
DOI: 10.1073/pnas.77.8.4813
发表时间: 1980
影响因子: 11.1
作者:
Grisham,JW;Greenberg,DS;Kaufman,DG;Smith,GJ
通讯作者: Smith,GJ