The correlation between DNA adducts and chromosomal aberrations in the target organ of benzidine exposed, partially-hepatectomized mice.
The correlation between DNA adducts and chromosomal aberrations in the target organ of benzidine exposed, partially-hepatectomized mice.
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暴露于联苯胺的部分肝切除小鼠靶器官中 DNA 加合物与染色体畸变之间的相关性。
DOI：
10.1093/carcin/8.12.1899
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发表时间：
1987
期刊：
影响因子：
4.7
通讯作者：
Legator,MS
中科院分区：
文献类型：
--
作者：
Talaska,G;Au,WW;WardJr,JB;Randerath,K;Legator,MS
开发了一个实验系统来测试联苯胺-DNA加合物水平与小鼠靶器官（肝脏）中染色体畸变之间的关联。进行2/3部分肝切除术（0 h），然后用联苯胺（0、7.8、19.5、38.2或97.8 mg/kg，i.p.）皮下植入琼脂包衣的50 mg 5-溴脱氧尿苷片剂（58 h）。以4 mg/kg i.p.（70 h）给予秋水仙胺，2 h后处死动物。对每只动物的肝脏进行分割，并将部分分配用于细胞遗传学和DNA加合物分析。DNA加合物用32P后标记技术分析。共有43只动物的DNA加合物和染色体畸变数据可用。联苯胺在肝脏（靶器官）中显示为一种有效的染色体断裂剂，而据报告其在骨髓中的活性较弱。在肝脏中发现的联苯胺-DNA加合物表现出线性剂量反应。加合物水平与畸变率的相关系数为0.43（P <0.05）。然而，大部分剩余差异是由于四个离群病例。当从数据集中删除这些病例并重复分析时，线性相关系数增加到0.74。当按剂量组分析数据时，相关性为0.91。这些数据支持致癌物-DNA加合物诱导染色体畸变以及可能的其他遗传毒性事件（包括瘤形成）的假设。
An experimental system was developed to test the association between benzidine—DNA adduct levels and chromosome aberrations in the target organ, the liver, of mice. A 2/3 partial hepatectomy was performed (0 h), then the animals were treated with benzidine (0, 7.8, 19.5, 38.2 or 97.8 mg/kg, i.p.) and an agar-coated 50 mg 5-bromodeoxyuridine tablet was implanted subcutaneously (58 h). Colcemid was given at 4 mg/kg i.p. (70 h), and the animals were sacrificed 2 h later. The liver from each animal was divided, with portions allocated for cytogenetics and DNA adduct analysis. DNA adducts were analyzed with the32P-postlabeling technique. DNA adduct and chromosomal aberration data were available on a total of 43 animals. Benzidine was shown to be a potent clastogen in liver, the target organ, as opposed to its reported weak activity in the bone marrow. A linear dose response was demonstrated for benzidine—DNA adducts found in the liver. The correlation between adduct levels and aberrations in individual animals was 0.43 (P< 0.05). However, most of the residual variance was due to four outlying cases. When these cases were removed from the data set and the analysis repeated, the linear correlation coefficient increased to 0.74. When the data were analyzed by dose groups, the correlation was 0.91. These data support the hypothesis that carcinogen—DNA adducts are responsible for the induction of chromosomal aberrations, and perhaps other genotoxic events, induding neoplasia.