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高血压与致癌物诱导的人类淋巴细胞非程序性DNA合成、DNA致癌物结合及染色体畸变有关。

High blood pressure related to carcinogen-induced unscheduled DNA synthesis, DNA carcinogen binding, and chromosomal aberrations in human lymphocytes.

作者信息

Pero R W, Bryngelsson C, Mitelman F, Thulin T, Nordén A

出版信息

Proc Natl Acad Sci U S A. 1976 Jul;73(7):2496-500. doi: 10.1073/pnas.73.7.2496.

Abstract

Unscheduled DNA synthesis (excision-repair) of N-acetoxy-2-acetylaminofluorene (NA-AAF) damage to the DNA of human lymphocytes was determined quantitatively for 92 individuals with diastolic blood pressures ranging from 65 to 120 mm of Hg (8,7 to 16 kPa). Measurements of NA-AAF-induced repair synthesis (incorporation of[3H]thymidine in the presence of 10 mM hydroxyurea) showed linear increase with the blood pressure in the individuals under study. Concurrent determinations for the levels of 3H-labeled 7,12-dimethyl-benz[a]anthracene bound to the DNAs of lymphocytes after 18 hr of culturing have shown that increased amounts of DNA bound carcinogen were linearly proportional to increased NA-AAF-induced repair synthesis values, and therefore were correlated to high blood pressure. The number of NA-AAF-induced chromosomal abberations in lymphocytes increased linearly with the diastolic blood pressures of the individuals. High NA-AAF-induced repair synthesis values also tended to be associated with increased NA-AAF-induced chromosomal damage. Together, these results suggest that individuals with elevated blood pressures have a greater potential for accumulating DNA damage, because of an increased chemical reactivity of lymphocytes to carcinogen exposure, than do individuals with normal blood pressure.

摘要

对92名舒张压在65至120毫米汞柱(8.7至16千帕)之间的个体,定量测定了N - 乙酰氧基 - 2 - 乙酰氨基芴(NA - AAF)对人淋巴细胞DNA造成的非程序性DNA合成(切除修复)。对NA - AAF诱导的修复合成(在10毫摩尔羟基脲存在下[3H]胸腺嘧啶的掺入)的测量表明,在所研究的个体中,其随血压呈线性增加。对培养18小时后与淋巴细胞DNA结合的3H标记的7,12 - 二甲基苯并[a]蒽水平的同时测定表明,与DNA结合的致癌物数量增加与NA - AAF诱导的修复合成值增加呈线性比例,因此与高血压相关。NA - AAF诱导的淋巴细胞染色体畸变数量随个体舒张压呈线性增加。NA - AAF诱导的高修复合成值也往往与NA - AAF诱导的染色体损伤增加有关。总之,这些结果表明,与血压正常的个体相比,血压升高的个体由于淋巴细胞对致癌物暴露的化学反应性增加,积累DNA损伤的潜力更大。

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