Soluble vs insoluble hexavalent chromate. Relationship of mutation to in vitro transformation and particle uptake.
Soluble vs insoluble hexavalent chromate. Relationship of mutation to in vitro transformation and particle uptake.
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可溶性与不溶性六价铬酸盐。
DOI：
10.1007/bf02917290
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发表时间：
1989
影响因子：
3.9
通讯作者：
Landolph,JR
中科院分区：
文献类型：
--
作者：
Patierno,SR;Landolph,JR
研究了可溶性cacro4和不溶性pbcro4诱导中国仓鼠卵巢细胞6-硫鸟嘌呤（碱基置换、缺失、添加和移位突变）或瓦巴因（碱基置换突变）抗性突变和C3H/101/2小鼠胚胎细胞形态转化的效果。cacro4诱导了6-硫鸟嘌呤耐药性的剂量依赖性细胞毒性和突变，但没有诱导乌阿巴因抗性突变或形态转化。高剂量的cacro4诱导10T1/2细胞转化为脂肪细胞，但这种细胞衍生的细胞系没有转化。在两种突变试验中，pbcro4都没有致突变性，但诱导了剂量依赖性、低频率的焦点形成。从这些病灶建立的细胞系的饱和密度增加了3 - 5倍，在软琼脂糖中生长，并且在裸鼠中具有致瘤性。慢性暴露于cacro4或pbcl2不诱导转化，pbcl2即使在急性细胞毒性浓度下也无活性，连续使用cacro4和pbcl2治疗也不诱导转化。光镜和扫描电镜显示pbcro4颗粒逐渐被细胞质吞噬，与颗粒接触的细胞广泛空泡化。液泡内未见颗粒。我们认为pbcro4的内化和相关的细胞应激反应可能与pbcro4诱导的10T1/2细胞的肿瘤转化有关。
Soluble CaCrO4and insoluble PbCrO4were tested for induction of mutation to 6-thioguanine (base-substitution, deletion, addition, and frameshift mutations) or ouabain (base-substitution mutations) resistance in Chinese hamster ovary cells and morphological transformation in C3H/101/2 mouse embryo cells. CaCrO4induced dose-dependent cytotoxicity and mutation to 6-thioguanine resistance, but did not induce mutation to ouabain resistance or morphological transformation. Highly cytotoxic amounts of CaCrO4induced conversion of 10T1/2 cells to adipocytes, but cell lines derived from such cells were not transformed. PbCrO4was not mutagenic in either mutation assay but induced a dose-dependent, low frequency of focus formation. Cell lines established from these foci had a 3–5-fold increased saturation density, grew in soft agarose, and were tumorigenic in nude mice. Chronic exposure to CaCrO4or PbCl2did not induce transformation, PbCl2was inactive even at acutely cytotoxic concentrations, and sequential treatments with CaCrO4and PbCl2did not induce transformation. Light and scanning electron microscopy showed progressive cytoplasmic engulfment of PbCrO4particles and extensive vacuolization of cells in contact with the particles. No particles were observed inside of vacuoles. We suggest that internalization of PbCrO4and the associated cellular stress response may be related to PbCrO4-induced neoplastic transformation of 10T1/2 cells.