Progression-linked properties of specific-lesion cell populations from 7,12-dimethylbenz[a]anthracene-exposed rat tracheal implants.
Progression-linked properties of specific-lesion cell populations from 7,12-dimethylbenz[a]anthracene-exposed rat tracheal implants.
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来自暴露于 7,12-二甲基苯并[a]蒽的大鼠气管植入物的特定病变细胞群的进展相关特性。
DOI：
10.1093/carcin/7.7.1165
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发表时间：
1986
期刊：
影响因子：
4.7
通讯作者：
Johnston,WW
中科院分区：
文献类型：
--
作者：
Marchok,AC;Huang,SF;Martin,DH;Johnston,WW
本研究的目的是确定体内气管上皮肿瘤进展的形态表达与从同一气管分离的致癌物改变的细胞群所表达的增强的体外生长自主性之间是否存在任何关系。大鼠气管植入物暴露于2 0 0μg 7，12二甲基苯并[a]菲蜂蜡微丸2周或4周。在先前报道的这项研究的第一阶段(1)，在暴露开始后的2、6和9个月，对致癌物质改变的细胞群体的数量进行了量化，这些细胞群体是通过在细胞培养中不需要外源性丙酮酸和胰岛素来鉴定的。在细胞培养前，将预先暴露的气管植入物置于器官培养中24小时，收集培养液中的脱落细胞进行细胞病理学诊断，以鉴定损伤情况。尽管暴露2周的气管在9个月时没有出现明显的非典型病变，但从该暴露组获得的少数传代细胞群(∼1/气管)的生长自主性逐渐增强。这一点体现在为测试裸鼠的锚定非依赖生长和致瘤性而扩大种群所需的培养时间的减少。与锚地无关的生长在2-6个月期间显著增加，从25%增加到80%，然后在9个月时增加到100%。致瘤性没有表现出增加。在暴露于DMBA的4周组中，74%的大量可培养细胞群(∼5.0/气管)在2个月时已经表现出贴壁无关的生长。这一比例在6个月和9个月时增加到94%-100%。成瘤细胞数量的逐渐增加也清晰可见。2个月后，接种到裸鼠体内的细胞群中有26%形成了肿瘤。这一数字在6个月和9个月时分别从45%增加到61%。在开始为期4周的DMBA暴露2个月后，取下的气管碎片没有明显的非典型病变。在6个月时发现一个明显的非典型性，在9个月时发现5个明显的不典型病变和2个原位癌。从含有这些病变的外植体中获得的细胞群体显示出很高的生长自主性，例如锚定无关的生长和肿瘤的形成，表明这些特性与肿瘤发展的不断演变的形态表现之间存在密切的关系。
The purpose of this study was to determine whether there are any relationships between the morphological expressions of the progression of neoplasia in tracheal epitheliumin vivo, and the increasedin vitrogrowth autonomy expressed by carcinogen-altered cell populations isolated from the same tracheas. Rat tracheal implants were exposed for 2 weeks or 4 weeks to 200 μg 7, 12-dimethylbenz[a]anthracene (DMBA) — beeswax pellets. In the first phase of this study reported earlier (1), the numbers of carcinogen-altered cell populations, identified by their lack of need for exogenous Pyruvate and insulin for survival in ceil culture, were quantitated 2, 6 and 9 months after the start of the exposures. Before generating the cell cultures, lesions on the pieces of pre-exposed tracheal implants were identified by placing them in organ culture for 24 h and collecting the exfoliated cells from the medium for diagnostic cytopathology. Although the pieces of 2-week DMBA-exposed tracheas had not developed any markedly atypical lesions by 9 months, there was a progressive increase in the growth autonomy of the small number of subculturable cell populations (∼ 1/trachea) obtained from this exposure group. This was seen in the decreased time needed in culture to expand the population for testing anchorage-independent growth and tumorigenicity in nude mice. Also, anchorage-independent growth was markedly enhanced from 25 to 80% between 2 and 6 months and then to 100% at 9 months. Tumorigenicity did not show an increase. In the 4-week DMBA-exposed group, 74% of the large number of sub-culturable cell populations (∼5.0/trachea) already showed anchorage-independent growth at 2 months. This percentage increased to 94–100% at 6 and 9 months. A progressive increase in tumorigenic cell populations was also clearly seen. At 2 months, 26% of the cell populations inoculated into nude mice formed tumors. This number increased from 45 to 61% at 6 and 9 months, respectively. The pieces of tracheas taken at 2 months after the start of the 4-week DMBA exposure had no markedly atypical lesions. At 6 months one marked atypia was detected, and at 9 months five markedly atypical lesions and two carcinomas in situ were present. The cell populations derived from the explants harboring these lesions showed a high incidence of growth autonomy, e.g. anchorage-independent growth and tumor formation, indicating a close relationship between these properties and the evolving morphological manifestations of tumor development.