Scinicariello Franco, Feroe Aliya G, Attanasio Roberta
Division of Toxicology and Human Health Sciences, Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA 30341, USA.
Department of Biology, Bowdoin College, Brunswick, ME, USA.
EBioMedicine. 2016 Apr;6:96-102. doi: 10.1016/j.ebiom.2016.02.027. Epub 2016 Feb 18.
The International Agency for Research on Cancer classified the di-2-ethylhexyl phthalate (DEHP) as "possibly carcinogenic to humans". In vitro studies reported that phthalate exposure resulted in induction of several nuclear transcription factors that are activators of telomerase reverse transcriptase (TERT) and telomerase activity of the human telomerase complex. The objective of this study was to determine whether there is an association between urinary phthalate metabolites [mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-(2-ethyl)-hexyl phthalate (MEHP), and mono-benzyl phthalate (MBzP) and leukocyte telomere length (LTL) in the adult population of the National Health and Nutrition Examination Survey (NHANES) 1999-2002 (n=2472). After adjustment for potential confounders, participants in the 3rd and 4th quartiles of urinary MEHP had statistically significantly longer LTL (5.34%, 95% CI: 1.31, 9.53; and 7.14%, 95% CI: 2.94, 11.63; respectively) compared to the lowest quartile, with evidence of a dose-response relationship (p-trend=0.01). The association remained when the analyses were stratified by age groups (20-39years, 40-59years, and 60years and older), and sex. Furthermore, MBP and MBzP were associated with higher LTL in older participants. The age independent association between longer LTL and MEHP (a metabolite of DEHP) might suggest a possible role of MEHP as tumor promoter.
国际癌症研究机构将邻苯二甲酸二(2-乙基己基)酯(DEHP)归类为“对人类可能致癌”。体外研究报告称,邻苯二甲酸盐暴露会诱导几种核转录因子,这些因子是端粒酶逆转录酶(TERT)的激活剂以及人类端粒酶复合物的端粒酶活性。本研究的目的是确定在1999 - 2002年美国国家健康与营养检查调查(NHANES)的成年人群(n = 2472)中,尿邻苯二甲酸盐代谢物[邻苯二甲酸单乙酯(MEP)、邻苯二甲酸单丁酯(MBP)、邻苯二甲酸单(2-乙基)己酯(MEHP)和邻苯二甲酸单苄酯(MBzP)]与白细胞端粒长度(LTL)之间是否存在关联。在对潜在混杂因素进行调整后,尿MEHP处于第三和第四四分位数的参与者与最低四分位数相比,LTL在统计学上显著更长(分别为5.34%,95%置信区间:1.31,9.53;以及7.14%,95%置信区间:2.94,11.63),有剂量反应关系的证据(p趋势 = 0.01)。当按年龄组(20 - 39岁、40 - 59岁以及60岁及以上)和性别分层分析时,该关联依然存在。此外,MBP和MBzP与老年参与者中更长的LTL相关。LTL延长与MEHP(DEHP的一种代谢物)之间与年龄无关的关联可能表明MEHP可能具有肿瘤促进作用。