Organochlorine pesticide content of breast adipose tissue from women with breast cancer and control subjects
Organochlorine pesticide content of breast adipose tissue from women with breast cancer and control subjects
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DOI：
10.1093/jnci/92.9.750
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发表时间：
2000-05-03
影响因子：
10.3
通讯作者：
Glaspy, JA
中科院分区：
文献类型：
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作者：
Bagga, D;Anders, KH;Glaspy, JA
作为杀虫剂的有机氯化合物可能与环境诱发的乳腺癌有关的说法是基于几项观察得出的。DDT[2,2 -二（对氯苯）- 1,1,1 -三氯乙烷]、其代谢物DDE[1,1 -二氯- 2,2 -二（对氯苯）乙烯]、类似农药和相关化学品（PCBs[多氯联苯]和PBBs[多溴联苯]）是已知的动物致癌物质（1,2）。DDT和多氯联苯都被证明是肿瘤促进剂(2)，并具有雌激素活性(3)。值得注意的是，一些研究（4-6）表明，有机氯可能抑制而不是促进肿瘤生长，甚至可能具有抗雌激素作用。由于有机氯在环境中的半衰期长，代谢效率低，在脂质中的溶解度高，导致在脂肪组织中的长期封存，因此在环境和人体组织中无处不在。然而，由于滴滴涕自1972年以来在美国已被禁止使用，滴滴涕及其代谢物在人群中的总体负担随着时间的推移而下降。对血清或脂肪组织中有机氯水平的病例对照研究（7-21）得出了关于接触这些化学物质与乳腺癌之间关系的相互矛盾的数据。Falck等人（14）进行的一项初步研究显示，癌症妇女（n 20）的乳腺脂肪组织中滴滴涕及其代谢物DDE和多氯联苯的浓度比乳腺良性疾病妇女（n 20）高50%。据估计，暴露在最高水平的妇女的相对风险约为3。虽然是初步的，但这些从小样本中获得的结果表明，这些有机氯在乳腺癌的病因中起作用。相比之下，一项规模更大的欧洲病例对照研究（10）利用臀脂肪组织，发现较高的有机氯含量与乳腺癌之间没有关联。在这项研究中，据我们所知，我们进行了迄今为止报道的对乳房脂肪组织中有机氯含量的最大研究。研究人群来自加利福尼亚州伍德兰希尔斯的凯撒永久医疗中心，时间为1995年1月至1996年12月。该研究得到了Kaiser Permanente医疗保健计划机构审查委员会的批准。所有患者被连续招募并给予书面知情同意纳入研究。在研究的146名女性中，有73名患有乳腺癌。对照组包括73名接受乳房缩小成形术的妇女。从医疗记录中获得患者的年龄、身高、体重、更年期状况和乳腺癌家族史等信息。活检时，采集乳腺脂肪组织0.2-1.0 g进行有机氯分析（18）。为了测定乳腺脂肪组织中的滴滴涕及其代谢物，使用微量天平准确称重200-300毫克脂肪组织，用甲醇（2毫升）处理，并用2.5毫升二乙醚和己烷（1:1）混合物提取三次。联合提取物在氮气下还原至0.5 mL，在2.5 g Florisil色谱柱（Supelco, Bellefonte， PA）上进行色谱。采用Florisil柱层析法，按照美国环境保护署的方法分离农药残留。洗脱两个馏分；第一个（13 mL）含有非极性残留物（包括DDE和DDD[1,1 -二氯- 2,2 -双（对氯苯）乙烷]），第二个(13 mL 6%二乙醚-己烷…
The suggestion that organochlorine compounds used as pesticides may be related to environment-induced breast cancer has been based on several observations. DDT [2, 2-bis (p-chlorophenyl)-1, 1, 1-trichloroethane], its metabolite DDE [1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethylene], similar pesticides, and related chemicals (PCBs [polychlorinated biphenyls] and PBBs [polybrominated biphenyls]) are known animal carcinogens (1, 2). Both DDT and PCBs have been shown to be tumor promoters (2) and to have estrogenic activity (3). It is important to note that some studies (4–6) have suggested that organochlorines may inhibit rather than promote tumor growth and may even have antiestrogenic effects. Organochlorines have become ubiquitous in the environment and in human tissues because of their long half-life in the environment, their inefficient metabolism, and their high solubility in lipids, which leads to longterm sequestration in adipose tissues. However, since the use of DDT has been banned in the United States since 1972, the total-body burden of DDT and of its metabolites in the population has fallen with time.Case–control studies of organochlorine levels in serum or adipose tissue (7–21) have yielded conflicting data regarding the connection between exposure to these chemicals and breast cancer. A pilot study conducted by Falck et al.(14) showed 50% higher concentrations of DDT, of its metabolite DDE, and of PCBs in mammary adipose tissue from women with cancer (n 20) compared with women with benign breast disease (n 20). A relative risk of approximately 3 was estimated for women in the highest tertile of exposure. Although preliminary, these results obtained from a small sample size suggested a role of these organochlorines in the causation of breast cancer. In contrast, a much larger European case–control study (10), which utilized gluteal adipose tissue, found no association between higher organochlorine content and the presence of breast cancer. In this study, we carried out, to our knowledge, the largest study of the organochlorine content of breast adipose tissue reported to date. The study population was derived from the Kaiser Permanente Medical Center in Woodland Hills, CA, during the period from January 1995 through December 1996. The study was approved by the Institutional Review Board of the Kaiser Permanente Medical Care Program. All patients were consecutively recruited and gave written informed consent to be included in the study. Of the 146 women studied, 73 had breast cancer. The control group comprised 73 women undergoing reduction mammoplasty for mastomegaly. Information regarding the patient’s age, height, weight, menopausal status, and family history of breast cancer was obtained from the medical records. At the time of biopsy, 0.2–1.0 g of breast adipose tissue was collected for organochlorine analysis (18). For the determinations of DDT and its metabolites in the breast adipose tissues, 200–300 mg of adipose tissue was accurately weighed with the use of a microbalance, treated with methanol (2 mL), and extracted three times with 2.5 mL of a mixture of diethylether and hexane (1: 1). The combined extracts were reduced to 0.5 mL under nitrogen and chromatographed on a 2.5-g Florisil column (Supelco, Bellefonte, PA). The use of the Florisil column chromatography was in accordance with the method of the US Environmental Protection Agency to separate pesticide residues. Two fractions were eluted; the first (13 mL of hexane) contained nonpolar residues (including DDE and DDD [1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethane]), and the second (13 mL of 6% diethylether–hexane …