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R E S E A R C H Proteomics sheds light on dioxin toxicity
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duced. To verify this result, the researchers cultured human hepatocellular carcinoma (HepG2) cells in the presence of Exposure to dioxins, particularly the low concentrations of TCDD. AFP and almost toxic congener, 2,3,7,8-tetrachlorobumin mRNA levels were determined by dibenzo-p-dioxin (TCDD), is known to reverse-transcription PCR, and the excause reproductive and developmental pression levels of the two proteins were abnormalities, as well as immunological determined by Western blotting. As exand hormonal changes, in humans. Now, pected, both mRNA and protein exproteomics researchers have found evipression levels of albumin dedence that TCDD exposure creased and those of AFP may also lead to other serious 2500 increased. health problems, including Normal Normal 2000 “The decrease in the albuliver disease and cancer. Dioxin Dioxin min expression in the HepG2 Although dioxin contami1500 cell culture with TCDD showed nation in the environment has 1000 that a decrease in the albumin been declining during the past level in the blood is solely due 30 years, several studies indi500 to reduced expression ability of cate that humans have been 0 1 2 3 4 5 6 7 liver cells,” says Kim. This is exposed to dioxins primarily Protein number important because the workers through diet, particularly Overexpressed. Seven proteins were found to be overexpressed in humans with low albumin levels were foods that are high in animal exposed to TCDD compared with those found in the normal population. the ones who had worked at fat. Several individuals have Protein numbers refer to (1) AFP, (2) pre-albumin, (3) fibrinogen A chain the incineration facility the also been exposed through precursor, (4) XAP-5, (5) human rab GDI, (6) follistatin, and (7) fibronectin. longest (>7 yr). “Although canoccupational and accidental cer was not detected yet, the routes. loss of the ability to produce albumin in those proteins that exhibited changes The expression of dioxin-regulated [the] liver may be in progress,” explains by MALDI TOFMS. They identified proteins is believed to cause the adverse Kim. seven overexpressed proteins in the effects associated with exposure to dioxThe results of the study also shed TCDD-exposed blood samples. Alins. To investigate this possibility, Chanlight on cross-species differences. Kim though they did see some variability in Wha Kim and colleagues at Korea Univerand colleagues previously examined proprotein expression levels in the exposed sity examined changes in the expression teins in the plasma (Proteomics 2003, 3, samples, “those of the workers were siglevels of plasma proteins caused by expo2393–2401) and liver of rats exposed to nificantly different from those of the sure to TCDD in municipal waste incinerTCDD ( J. Proteome Res. 2005, 4, 335–343). healthy group,” says Kim. ation workers. The results, which are reThey identified one newly expressed proAmong the identified proteins were a ported in this issue of JPR (pp 1248–1255), tein and three overexpressed proteins in group related to liver disease and cellular could help epidemiologists better underrat plasma. In addition, they identified proliferation during cancer. These prostand the mechanisms underlying dioxin two newly expressed proteins and seven teins included alpha-feto protein (AFP), toxicity. overexpressed proteins in rat liver tissue. fibronectin, pre-albumin, fibrinogen A Kim and colleagues analyzed blood Interestingly, none of the proteins were chain precursor, and XAP-5. “An elevated samples from 31 workers who had been found in both humans and rats. level of AFP suggests the presence of eiemployed at a waste incineration facility The proteins identified in the human ther a primary liver cancer or germ cell in Seoul, Korea, for an average of 7 yr. dioxin study also appear to be specific to tumor,” says Kim. One newly expressed The concentration of dioxins in the air TCDD exposure. The researchers previprotein, adrenomedulin binding protein at the facility was determined to be ously investigated changes in plasma (AMBP), was also identified in the TCDD100 higher than that measured in amprotein levels in humans caused by expoexposed blood samples. “Because AMBP bient air in Seoul. The researchers also sure to other toxic chemicals, including is a protein related to survival of cancer analyzed control blood samples from 33 PAHs and benzene (Proteomics 2003, 3, cells from apoptosis and indirect suppatients who had received an annual 2402–2411; 2004, 4, 3505–3513). Exposure pression of immune response, the new checkup at a hospital in Seoul. to these chemicals “did not affect the exexpression of AMBP could [signal] the deBecause no standard in vivo method pression levels of the same proteins in velopment of cancer cells,” says Kim. exists for evaluating dioxin exposure in human plasma as dioxin,” says Kim. In 15 of the 31 workers, expression humans, Kim and colleagues indirectly —Britt E. Erickson levels of albumin were significantly redetermined dioxin exposure by measurRelative intensity
ing the levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs), 1-hydroxypyrene, and 2-naphthol. The levels of these metabolites in the workers were significantly higher than those in the control subjects. The researchers determined changes in plasma proteins associated with dioxin exposure by 2DE and identified
© 2005 American Chemical Society
Journal of Proteome Research • Vol. 4, No. 4, 2005
1049
