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多氯联苯与白细胞端粒长度:对 1999-2002 年 NHANES 的分析。

Polychlorinated Biphenyls and Leukocyte Telomere Length: An Analysis of NHANES 1999-2002.

机构信息

Division of Toxicology and Human Health Sciences, Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA 30341, USA.

出版信息

EBioMedicine. 2015 Nov 19;2(12):1974-9. doi: 10.1016/j.ebiom.2015.11.028. eCollection 2015 Dec.

Abstract

Polychlorinated biphenyls (PCBs) induce the expression of the proto-oncogene c-myc which has a role in cellular growth and proliferation programs. The c-myc up-regulates the telomerase reverse transcriptase which adds the telomeres repeating sequences to the chromosomal ends to compensate for the progressive loss of telomeric sequence. We performed multivariate linear regression to analyze the association of PCBs, polychlorinated dibenzo-p-dioxins, and 1,2,3,4,6,7,8-heptachlorodibenzofuran with leukocyte telomere length (LTL) in the adult population (n = 2413) of the National Health and Nutrition Examination Survey 1999-2002. LTL was natural log-transformed and the results were re-transformed and presented as percent differences. Individuals in the 3rd and 4th quartiles of the sum of PCBs were associated with 8.33% (95% CI: 4.08-13.88) and 11.63% (95% CI: 6.18-17.35) longer LTLs, respectively, compared with the lowest quartile, with evidence of a dose-response relationship (p-trend < 0.01). The association of the sum PCBs with longer LTL was found in both sexes. Additionally, 1,2,3,4,6,7,8-heptachlorodibenzofuran and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin were associated with longer LTL. The age independent association between longer LTL and environmental exposures to PCBs, 1,2,3,4,6,7,8-heptachlorodibenzofuran and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin may support a role as tumor promoter of these compounds. Further studies to evaluate the effect of these compounds on LTL are needed to more fully understand the implications of our finding.

摘要

多氯联苯 (PCBs) 诱导原癌基因 c-myc 的表达,该基因在细胞生长和增殖程序中起作用。c-myc 上调端粒酶逆转录酶,该酶将端粒重复序列添加到染色体末端,以补偿端粒序列的逐渐丢失。我们进行了多元线性回归分析,以研究 1999-2002 年全国健康与营养调查 (NHANES) 中成人人群 (n = 2413) 中 PCBs、多氯二苯并对二恶英和 1,2,3,4,6,7,8-七氯二苯并呋喃与白细胞端粒长度 (LTL) 的关联。LTL 进行自然对数转换,结果经转换后以百分比差异呈现。与最低四分位相比,PCBs 总和处于第 3 和第 4 四分位的个体分别与 LTL 长 8.33%(95%CI:4.08-13.88)和 11.63%(95%CI:6.18-17.35),具有剂量反应关系 (p-trend < 0.01)。在两性中均发现 PCBs 总和与 LTL 较长相关。此外,1,2,3,4,6,7,8-七氯二苯并呋喃和 1,2,3,6,7,8-六氯二苯并对二恶英与 LTL 较长相关。环境暴露于 PCBs、1,2,3,4,6,7,8-七氯二苯并呋喃和 1,2,3,6,7,8-六氯二苯并对二恶英与 LTL 较长之间的独立于年龄的关联可能支持这些化合物作为肿瘤促进剂的作用。需要进一步研究这些化合物对 LTL 的影响,以更全面地了解我们研究结果的意义。

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