2-STAGE CARCINOGENESIS WITH RAT EMBRYO CELLS IN TISSUE-CULTURE

2-STAGE CARCINOGENESIS WITH RAT EMBRYO CELLS IN TISSUE-CULTURE
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DOI:
10.1038/bjc.1977.113
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发表时间:
1977-01-01
影响因子:
8.8
通讯作者:
CHOUROULINKOV, I
CHOUROULINKOV, I
中科院分区:
医学1区
文献类型:
--
作者:
LASNE, C;GENTIL, A;CHOUROULINKOV, I

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用苯并(a)芘(BaP)、7,12-二甲基苯并(a)蒽(DMBA)或苯并(e)芘(BeP)作为转化剂,以佛波酯(TPA)或巴豆油(Cr.Oil)作为促进剂,研究了大鼠胚胎成纤维细胞的体外转化。用于评估体外转化的标准是在液体培养基中的克隆效率、异常细胞形态和在s.c.接种新生大鼠。在对照细胞中保持较低的克隆效率在处理组中增加到不同程度。转化发生在所有组中,但最早发生在启动和促进的细胞中。用DMBA或BaP启动,用TPA或Cr.Oil促进,导致最早获得恶性肿瘤。体外细胞转化和恶性潜能的获得之间存在相关性,体外化合物的致癌作用和它们在体内的作用之间存在相关性,但克隆效率不是体外转化或恶性的可靠指标。在大多数情况下,在体外转化出现之前收购的恶性肿瘤,但在2例发生后。研究还表明,BeP在体内是肿瘤引发剂,在体外也以这种方式起作用。从这些结果和体内2阶段致癌作用的讨论中得出的结论是,2阶段致癌作用可以在组织培养中重现。这一模型可能有助于研究化学致癌作用的启动和促进过程。
Transformation of rat embryo fibroblasts in vitro was investigated using initiation with benzo(a)pyrene (BaP), 7,12-dimethylbenz(a)anthracene (DMBA) or benzo(e)pyrene (BeP) and promotion with phorbol ester (TPA) or croton oil (Cr.Oil). The criteria used to assess in vitro transformation were the efficiency of cloning in liquid medium, abnormal cellular morphology and the development of malignant tumors following s.c. inoculation of newborn rats. The cloning efficiency, which remained low in the control cells, was increased to a variable extent in the treated groups. Transformation occurred in all groups, but occurred earliest in cells that were initiated and promoted. Initiation with DMBA or BaP and promotion with TPA or Cr.Oil led to the earliest acquisition of malignancy. Correlations were found between the transformation of cells in vitro and the acquisition of malignant potential, and between the carcinogenic action of the compounds in vitro and their action in vivo, but cloning efficiency was not a reliable indicator of in vitro transformation or malignancy. In most cases in vitro transformation appeared to precede the acquisition of malignancy, but in 2 cases it occurred later. The studies also show that BeP, which is a tumor initiator in vivo, also acts in this way in vitro. The conclusion drawn from a discussion of these results and of 2 stage carcinogenesis in vivo is that 2 stage carcinogenesis can be reproduced in tissue culture. This model may be useful in studies of those mechanisms of chemical carcinogenesis that involve the processes of initiation and promotion.