t(14;18) translocations in lymphocytes of healthy dioxin-exposed individuals from Seveso, Italy.
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Pesatori, Angela C.
Patterson, Donald G.
Bertazzi, Pier Alberto
Landi, Maria Teresa
MetadataShow full item record
AbstractDioxin 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 > or =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.
CitationCarcinogenesis 2006, 27 (10):2001-2007
DescriptionBiomarkers of exposure & early effects: field studiesBiomarker:t(14;18) translocationExposure/effect represented:dioxin (TCDD)Study design:cross-sectionalStudy size:211 healthy, 101 individuals with skin disorder, 72 caucasians with high levels of TCDD(>10ppt) and 72 with lowblevels of TCDD(<10ppt)Analytical technique:real-time quantitative PCR, gel electrophoresis, dioxin assayTissue/biological material/sample size:whole bloodRelationship with exposure or effect of interest (including dose-response):Plasma TCDD<10ppt Number of translocations 4.2/106 lymphocytes (CI95%, 2.9-6.2)Plasma TCDD<50ppt/>10ppt Number of translocations 8.1/106 lymphocytes (CI95%, 4.9-13.3)Plasma TCDD>50ppt/<475ppt Number of translocations 12.5/106 lymphocytes (CI95%, 7.4-21.1)Factors modulating biomarkers:smoking status>16y translocation frequency 12.6/106 lymphocytes, 95% CI 7.4-21.3smoking status<15y translocation frequency 5.2/106 lymphocytes, 95% CI 3.1-8.9, P=0.01. KEYWORDS CLASSIFICATION: Adolescent;Adult;biomarkers of exposure & effect: field studies;blood;Child;Child,Preschool;Chromosomes,Human,Pair 14;Chromosomes,Human,Pair 18;drug effects;Environmental Health;Epidemiology;field studies;Female;Hair Color;Humans;Infant;Italy;Lymphocytes;Male;Middle Aged;Research;toxicity;Tetrachlorodibenzodioxin;Translocation,Genetic;ultrastructure.