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苯-DNA加合物的研究及其在人类骨髓中的检测。

Investigation of benzene-DNA adducts and their detection in human bone marrow.

作者信息

Bodell W J, Levay G, Pongracz K

机构信息

Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143.

出版信息

Environ Health Perspect. 1993 Mar;99:241-4. doi: 10.1289/ehp.9399241.

Abstract

We have examined DNA adduct formation in HL-60 cells and human bone marrow treated with either hydroquinone or p-benzoquinone and have found that these treatments produce the same DNA adduct in both cell types. The DNA adduct level from these treatments varied from 0.05 to 7.5 adducts per 10(7) nucleotides as a function of treatment time and concentration for both compounds. Reaction of calf thymus DNA with p-benzoquinone produced three adducts as detected by 32P-postlabeling. These adducts have been identified as (3'-hydroxy)-3,N4-benzetheno-2'-deoxycytidine-3'-phosphate; (3'-hydroxy)-1,N6-benzetheno-2'-deoxyadenosine-3'-phosphate; and (3'-hydroxy)-1,N2-benzetheno-2'-deoxyguanosine-3'-phosphate. The DNA adduct formed in HL-60 cells did not correspond to any of the principal adducts formed in DNA reacted with p-benzoquinone, suggesting that cellular environment modifies DNA adduct production by p-benzoquinone. These studies demonstrate that DNA adduct formation occurs in human bone marrow treated with benzene metabolites and suggest that P1-enhanced 32P-postlabeling may be used to detect DNA adducts resulting from benzene exposure.

摘要

我们检测了用对苯二酚或对苯醌处理的HL-60细胞和人骨髓中的DNA加合物形成情况,发现这些处理在两种细胞类型中产生相同的DNA加合物。这些处理产生的DNA加合物水平随处理时间和两种化合物浓度的变化而在每10⁷个核苷酸0.05至7.5个加合物之间波动。通过³²P后标记检测到,小牛胸腺DNA与对苯醌反应产生了三种加合物。这些加合物已被鉴定为(3'-羟基)-3,N⁴-苯并乙撑-2'-脱氧胞苷-3'-磷酸;(3'-羟基)-1,N⁶-苯并乙撑-2'-脱氧腺苷-3'-磷酸;以及(3'-羟基)-1,N²-苯并乙撑-2'-脱氧鸟苷-3'-磷酸。HL-60细胞中形成的DNA加合物与对苯醌反应的DNA中形成的任何主要加合物均不对应,这表明细胞环境会改变对苯醌产生DNA加合物的情况。这些研究表明,在苯代谢物处理的人骨髓中会发生DNA加合物形成,并且表明P1增强的³²P后标记可用于检测苯暴露导致的DNA加合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/726b/1567040/0538f114a71b/envhper00412-0219-a.jpg

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