Malignant transformation of human fibroblast cell strain MSU-1.1 by (+-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene.

Malignant transformation of human fibroblast cell strain MSU-1.1 by (+-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene.
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(-)-7β,8α-二羟基-9α,10α-环氧-7,8,9,10-四氢苯并[a]芘对人成纤维细胞株MSU-1.1的恶性转化。

DOI:
10.1073/pnas.89.6.2237
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发表时间:
1992
影响因子:
11.1
通讯作者:
McCormick,JJ
McCormick,JJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Yang,D;Louden,C;Reinhold,DS;Kohler,SK;Maher,VM;McCormick,JJ

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MSU-1.1 细胞是一种近二倍体、核型稳定、无限寿命的人成纤维细胞菌株,用 (±)-7 beta,8 α-二羟基-9 α,10 α-环氧-7,8,9,10-四氢苯并[a]芘诱导病灶形成。分离出八个独立的病灶,并检查从它们发展而来的细胞株的恶性细胞特征。每个细胞在含有 1% 血清的培养基中生长到比 MSU-1.1 细胞更高的密度。 8 种中的 3 种在不添加生长因子的无血清培养基中快速生长,在琼脂糖中以 5-19% 的频率形成直径大于或等于 120 微米的集落,表现出遗传物质的损失,并且当注射到无胸腺小鼠中时,在 2-3 周内形成直径达到 6 毫米的肉瘤。一种产生高级肉瘤(逐渐生长的侵袭性肿瘤,表现出高有丝分裂活性);另外两种产生低级别肉瘤(有丝分裂活性较低的肿瘤),如果在动物体内放置超过 4 周,就会形成高级别恶性细胞的焦点区域。第四种细胞株仅在 2.5-3 个月后形成高级肉瘤,但所分析的肿瘤来源细胞显示出与上述三种恶性细胞株相同的生长特性,表现出遗传物质的损失,并且当重新注射到无胸腺小鼠体内时,产生了具有较短潜伏期的高级肉瘤。
Treatment of MSU-1.1 cells, a near-diploid, karyotypically stable, infinite life-span human fibroblast strain, with (+-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene induced focus formation. Eight independent foci were isolated and the cell strains developed from them were examined for characteristics of malignant cells. Each grew to a higher density in medium containing 1% serum than did the MSU-1.1 cells. Three of the eight grew rapidly in serum-free medium without added growth factors, formed colonies in agarose with diameters of greater than or equal to 120 microns at a frequency of 5-19%, exhibited loss of genetic material, and, when injected into athymic mice, formed sarcomas that reached 6 mm in diameter within 2-3 wk. One produced high-grade sarcomas (progressively growing, invasive tumors exhibiting high mitotic activity); the other two produced low-grade sarcomas (tumors with a lower degree of mitotic activity) that developed focal areas of high-grade malignant cells if left in the animals for greater than 4 wk. A fourth cell strain formed high-grade sarcomas only after 2.5-3 mo, but the tumor-derived cells analyzed showed the same growth properties as the three malignant cell strains described above, exhibited loss of genetic material, and, when reinjected into athymic mice, produced high-grade sarcomas with a short latency period.