t(14;18) translocations in lymphocytes of healthy dioxin-exposed individuals from Seveso, Italy
t(14;18) translocations in lymphocytes of healthy dioxin-exposed individuals from Seveso, Italy
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DOI：
10.1093/carcin/bgl011
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发表时间：
2006-10-01
期刊：
影响因子：
4.7
通讯作者：
Landi, Maria Teresa
中科院分区：
文献类型：
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作者：
Baccarelli, Andrea;Hirt, Carsten;Landi, Maria Teresa
在流行病学调查中，二恶英暴露与非霍奇金淋巴瘤（NHL）有关。NHL相关的t（14;18）易位可以在来自健康受试者的淋巴细胞中以低拷贝数检测到。暴露于NHL相关的致癌物，如二恶英或杀虫剂，可能会导致t（14;18）阳性克隆的扩增。我们调查了144名健康受试者中循环t（14;18）阳性淋巴细胞的患病率和频率，这些受试者来自暴露于二恶英的人群[血浆TCDD（2，3，7，8-四氯二苯并-对-二恶英）范围：< 1.7-475.0万亿分之一（p.p.t.）]在1976年意大利塞维索事故之后。通过高灵敏度实时定量聚合酶链反应测定外周血淋巴细胞DNA中的t（14;18）易位。我们发现，t（14;18）易位阳性细胞的频率，而不是患病率，随着血浆TCDD的增加而增加。其中t（14;在血浆TCDD < 10.0 p.p.t.的受试者中，t（14;18）易位/10（6）淋巴细胞的平均数为4.2 [95%置信区间（CI），2.9-6.2]，8.1（95% CI，4.9-13.3），血浆TCDD在50.0 - 475.0 p.p.t.之间的受试者为12.5（95% CI，7.4-21.1）。（P趋势= 0.003）。正如预期的那样，t（14; 18）频率与吸烟相关，在吸烟≥ 16年的受试者中最高（平均值= 12.6; 95%CI，7.4-21.3; P = 0.01）。在金发（P = 0.01）和浅色眼睛（P = 0.04）的个体中发现较高的t（14;18）患病率。t（14;18）-和年龄之间没有显著的联系，我们的研究结果表明二恶英暴露与循环中t（14;18）阳性细胞数量的增加有关。t（14;18）频率的这种变化是否是淋巴瘤风险升高的指标仍然是推测性的，需要进一步调查其对公共卫生的潜在影响。
Dioxin exposure has been associated with non-Hodgkin's lymphoma (NHL) in epidemiological investigations. The NHL-related t(14;18) translocations can be detected at a low copy number in lymphocytes from healthy subjects. Exposure to NHL-associated carcinogens, such as dioxin or pesticides, may cause expansion of t(14;18)-positive clones. We investigated prevalence and frequency of circulating t(14;18)-positive lymphocytes in 144 healthy subjects from a population exposed to dioxin [plasma TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) range: < 1.7-475.0 parts per trillion (p.p.t.)] after the Seveso, Italy, accident of 1976. t(14;18) translocations were measured in DNA from peripheral blood lymphocytes by high-sensitivity real-time quantitative polymerase chain reaction. We found that the frequency, but not the prevalence, of t(14;18) translocation-positive cells increased with increasing plasma TCDD. Among t(14;18)-positive subjects (n = 50;34.7%), the mean number of t(14;18) translocations/10(6) lymphocytes was 4.2 [95% confidence interval (CI), 2.9-6.2] in subjects with plasma TCDD < 10.0 p.p.t., 8.1 (95% CI, 4.9-13.3) in subjects with plasma TCDD between 10.0 and 50.0 and 12.5 (95% CI, 7.4-21.1) in subjects with plasma TCDD between 50.0 and 475.0 p.p.t. (P-trend = 0.003). As expected, t(14;18) frequency was associated with cigarette smoking and was highest in subjects who smoked for >= 16 years (mean = 12.6; 95% CI, 7.4-21.3; P = 0.01). Higher t(14;18) prevalence was found among individuals with fair hair color (P = 0.01) and light eye color (P = 0.04). No significant association between t(14;18)-and age was found. Our results show that dioxin exposure is associated with increased number of circulating t(14;18) positive cells. Whether this change in t(14;18) frequency is an indicator of elevated lymphoma risk remains speculative and needs further investigation for its potential impact on public health.