t(14;18) translocations in lymphocytes of healthy dioxin-exposed individuals from Seveso, Italy.
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 > 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.
EPOCA Research Center for Occupational, Clinical and Environmental Epidemiology, Department of Occupational and Environmental Health, University of Milan, IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Milan, Italy.
Andrea
A
Baccarelli
Carsten
C
Hirt
Angela C
AC
Pesatori
Dario
D
Consonni
Donald G
DG
Patterson
Pier Alberto
PA
Bertazzi
Gottfried
G
Dölken
Maria Teresa
MT
Landi
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D005260:Female; D006200:Hair Color; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D000072317:Polychlorinated Dibenzodioxins / Q000097:blood / Q000633:toxicity*; D014178:Translocation, Genetic
D000072317:Polychlorinated Dibenzodioxins