Induction of anchorage independence in human diploid foreskin fibroblasts by carcinogenic metal salts.
Induction of anchorage independence in human diploid foreskin fibroblasts by carcinogenic metal salts.
复制标题
致癌金属盐诱导人二倍体包皮成纤维细胞的锚定独立性。
作者：
K. Biedermann;J. Landolph
我们研究了是否砷，镍，铬化合物是人类致癌物可以诱导转化培养的原代人类二倍体包皮细胞（HFC）。所有测试的镍化合物，PbCrO 4，K2 Cr2 O 7，CrO 3，Na 2 HAsO 4，NaAsO 2和N-甲基-N '-硝基-N-亚硝基胍（MNNG）引起HFC中锚定非依赖性菌落的显著（p = 0.001）剂量依赖性诱导。KH_2AsO_4、CaCl_2、MnCl_2和Hg（CH_3CO_2）_2不诱导锚定独立性。最佳表达时间诱导锚定独立HFC观察早在11天后，用MNNG，Ni 3S 2，Ni（C2 H3 O2），或NiSO 4处理。来源于锚定非依赖性集落的细胞株在软琼脂中的接种效率比亲本群体高33至429倍，并且锚定非依赖性表型在8次传代中保持稳定，此时细胞衰老。来源于金属盐处理的细胞的锚定独立的细胞株不耐金属盐的细胞毒性，表明金属盐诱导，而不是选择锚定独立性。10个细胞株中的9个来自金属化合物或MNNG诱导的锚定非依赖性集落，显示出与未处理的人成纤维细胞相同或更低的饱和密度。这些细胞株都没有逃脱衰老或表现出明确的形态转化。MNNG（1微克/毫升）诱导锚定的独立性和突变的哇巴因抗性和6-硫鸟嘌呤抗性在HFC中，但浓度的Ni 2S 3诱导锚定的独立性没有诱导突变在HFC中的任何一个位点。这些结果表明，致癌金属盐诱导稳定的锚定独立性早在人二倍体包皮成纤维细胞，这种锚定独立性是独立的其他体外标记的成纤维细胞转化，如焦点形成或永生。金属盐诱导的锚定独立性，现在可以用来作为一种分析，研究致癌金属化合物在人类细胞中施加的遗传毒性的机制。
We studied whether arsenic, nickel, and chromium compounds that are human carcinogens could induce transformation of cultured primary human diploid foreskin cells (HFC). All nickel compounds tested, PbCrO4, K2Cr2O7, CrO3, Na2HAsO4, NaAsO2, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) caused significant (p = 0.001) dose-dependent inductions of anchorage-independent colonies in HFC. KH2AsO4, CaCl2, MnCl2, and Hg(CH3CO2)2 did not induce anchorage independence. Optimal expression times for induction of anchorage independence in HFC were observed as early as 11 days following treatment with MNNG, Ni3S2, Ni(C2H3O2), or NiSO4. Cell strains derived from anchorage-independent colonies showed 33 to 429-fold higher plating efficiencies in soft agar than parental populations, and the anchorage-independent phenotype was stable for eight passages, at which time cells senesced. Anchorage-independent cell strains derived from metal salt-treated cells were not resistant to the cytotoxicity of metal salts, indicating metal salts induced rather than selected for anchorage independence. Nine of 10 cell strains derived from metal compound- or MNNG-induced anchorage-independent colonies displayed the same or lower saturation densities than untreated human fibroblasts. None of these cell strains escaped senescence or showed definitive morphological transformation. MNNG (1 micrograms/ml) induced anchorage independence and mutation to ouabain resistance and 6-thioguanine resistance in HFC, but concentrations of Ni2S3 that induced anchorage independence did not induce mutation at either locus in HFC. These results demonstrate that carcinogenic metal salts induce stable anchorage independence early in human diploid foreskin fibroblasts, and this anchorage independence is independent of other in vitro markers of fibroblast transformation, such as focus formation or immortality. Metal salt induction of anchorage independence can now be used as an assay to study mechanisms of genotoxicity exerted by carcinogenic metal compounds in human cells.
登录
查看更多内容
铬与体内经重铬酸钠和氯化铬 (III) 处理的大鼠肝脏和肾脏的染色质和 DNA 的结合。
影响因子：
11.2
作者：
Cupo,DY;Wetterhahn,KE
通讯作者：
Wetterhahn,KE
C3H 10T 1/2 细胞化学诱导多步肿瘤转化的机制。
DOI：
--
发表时间：
1985
期刊：
Carcinogenesis; a comprehensive survey
影响因子：
--
作者：
Landolph,JR
通讯作者：
Landolph,JR
通过丙烷磺内酯诱导人成纤维细胞的锚定非依赖性生长。
影响因子：
11.2
作者：
Silinskas,KC;Kateley,SA;Tower,JE;Maher,VM;McCormick,JJ
通讯作者：
McCormick,JJ
体内用碳酸镍处理的大鼠肾脏和肝脏中的镍结合染色质、核酸和核蛋白。
影响因子：
11.2
作者：
Ciccarelli,RB;Wetterhahn,KE
通讯作者：
Wetterhahn,KE
X 射线诱导的染色体重排在人二倍体成纤维细胞的长期培养中持续存在。
影响因子：
11.2
作者：
Kano,Y;Little,JB
通讯作者：
Little,JB