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Biomedical subjects

A Bergman

Publications and source records attributed to A Bergman.

At least 55 records · Page 3Linked to original sources
PubMed2000

Biochemical and genetic interactions between Drosophila caspases and the proapoptotic genes rpr, hid, and grim.

In Drosophila melanogaster, the induction of apoptosis requires three closely linked genes, reaper (rpr), head involution defective (hid), and grim. The products of these genes induce apoptosis by activating a caspase pathway. Two very similar Drosophila caspases, DCP-1 and drICE, have been previously identified. We now show that DCP-1 has a substrate specificity that is remarkably similar to those of human caspase 3 and Caenorhabditis elegans CED-3, suggesting that DCP-1 is a death effector caspase. drICE and DCP-1 have similar yet different enzymatic specificities. Although expression of either in cultured cells induces apoptosis, neither protein was able to induce DNA fragmentation in Drosophila SL2 cells. Ectopic expression of a truncated form of dcp-1 (DeltaN-dcp-1) in the developing Drosophila retina under an eye-specific promoter resulted in a small and rough eye phenotype, whereas expression of the full-length dcp-1 (fl-dcp-1) had little effect. On the other hand, expression of either full-length drICE (fl-drICE) or truncated drICE (DeltaN-drICE) in the retina showed no obvious eye phenotype. Although active DCP-1 protein cleaves full-length DCP-1 and full-length drICE in vitro, GMR-DeltaN-dcp-1 did not enhance the eye phenotype of GMR-fl-dcp-1 or GMR-fl-drICE flies. Significantly, GMR-rpr and GMR-grim, but not GMR-hid, dramatically enhanced the eye phenotype of GMR-fl-dcp-1 flies. These results indicate that Reaper and Grim, but not HID, can activate DCP-1 in vivo.

Animals↗
PubMed2000

Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants which exert a variety of toxic effects in animals, including disturbances of sexual development and reproductive function. The estrogenic effects of PCBs may be mediated in part by hydroxylated PCB metabolites (PCB-OHs), but the mechanisms by which they are brought about are not understood. PCBs as well as PCB-Hs show low affinities for both alpha and beta estrogen receptor isoforms. In the present study we demonstrate that various environmentally relevant PCB-OHs are extremely potent inhibitors of human estrogen sulfotransferase, strongly suggesting that they indirectly induce estrogenic activity by increasing estradiol bioavailability in target tissues.

Biological Availability↗
PubMed2000

Influence of the consumption of fatty Baltic Sea fish on plasma levels of halogenated environmental contaminants in Latvian and Swedish men.

We examined the influence of widely varied consumption of fatty fish from the Baltic Sea and of age on plasma concentrations of polychlorinated biphenyls (PCBs), polychlorobiphenylols (OH-PCBs), 2, 2-bis(4-chlorophenyl)-1,1,1-trichloroethane (4,4'-DDT), 2, 2-bis(4-chlorophenyl)-1,1-dichloroethane (4,4'-DDE), 2,2',4, 4'-tetrabromodiphenyl ether (BDE-47), hexachlorobenzene (HCB), and pentachlorophenol (PCP) in Latvian and Swedish men. Both age and fish consumption were significantly correlated with the concentrations of [sigman]PCB, [sigman]OH-PCB, 4,4'-DDE, 4,4'-DDT, and HCB. In the case of BDE-47, no significant relationship with age was observed, and fish consumption had the largest relative effect on plasma concentrations of this contaminant. This relationship may be a result of exposure to BDE-47 having been more recent than that of PCBs and DDE, or because the half-life of BDE-47 may be shorter than that of PCB and DDE. Latvian men demonstrated higher plasma levels of DDE and DDT but lower levels of [sigman]PCB and PCP than did Swedish men. The corresponding levels of HCB and BDE-47 were similar in both countries. The Spearman's rank correlation coefficient obtained by comparing the level of the metabolite 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) to the combined levels of its parent compounds, 2,3,3',4, 4'-pentachlorobiphenyl (CB-105) and 2,3',4,4',5-pentachlorobiphenyl (CB-118), was higher than the median correlation coefficient obtained upon comparing the level of this metabolite to all other possible combinations of two PCB levels. No other increased correlation between metabolite and parent PCB concentration was observed.

Adult↗
PubMed1999

Napsin A, a member of the aspartic protease family, is abundantly expressed in normal lung and kidney tissue and is expressed in lung adenocarcinomas.

A pair of 35 kDa polypeptides (TAO1/TAO2) are expressed in more than 90% of all primary lung adenocarcinomas but not in other major malignancies. Mass spectrometry of tryptic peptides showed that TAO1/TAO2 is identical to napsin A, a recently described member of the aspartic proteinase family. The site of processing of pronapsin A to the mature form was located. Napsin expression was detected in human lung adenocarcinoma tumors, compatible with the marker nature of TAO1/TAO2 in the diagnosis of primary lung adenocarcinoma. This is important since identification of markers which can distinguish primary lung adenocarcinomas from distant metastases is desirable. Northern blot analysis showed expression of napsin also in normal lung and kidney tissue, and in situ hybridization showed expression in type II alveolar cells of the lung. This protease is concluded to have a specific functional role in the normal alveolar epithelium and is a candidate protease for the proteolytic processing of surfactant precursors.

Adenocarcinoma↗
PubMed1999

Analysis of polybrominated diphenyl ethers in Swedish human milk. A time-related trend study, 1972-1997.

A previously described method for analysis of organochlorine compounds in human milk was adopted for analysis of brominated diphenyl ethers (BDEs) substituted with three to six bromine atoms. Analytes were extracted from human milk with the lipophilic gel Lipidex 5000. Further purifications were performed on partly deactivated aluminum oxide and silica gel columns, followed by gel permeation chromatography. The concentrations of BDEs were determined by gas chromatography/mass spectrometry (GC/MS). The average recoveries of 2,2',4-triBDE (BDE-17), 2,4,4'-triBDE (BDE-28), 2,2',4,4'-tetraBDE (BDE-47), 2,3',4,4'-tetraBDE (BDE-66), 2,2,3,4,4'-pentaBDE (BDE-85), 2,2',4,4',5-pentaBDE (BDE-99), 2,2',4,4',6-pentaBDE (BDE-100), 2,2',4,4',5,5'-hexaBDE (BDE-153), and 2,2',4,4',5,6'-hexaBDE (BDE-154) added to the samples before extraction ranged from 86% to 102%. Pooled samples of breast milk, collected at eight time periods between 1972 and 1997, were analyzed for PBDEs. BDE-47 was the most abundant PBDE congener in all samples. In total, eight PBDE congeners were identified in the milk. The sum of the concentrations of BDE congeners in human milk increased from 0.07 to 4.02 ng/g lipids during the 25-yr period studied.

Adult↗
PubMed1999

Cytotoxicity and aromatase (CYP19) activity modulation by organochlorines in human placental JEG-3 and JAR choriocarcinoma cells.

The human placental JEG-3 and JAR choriocarcinoma cell lines have been used as placental models for the study of aromatase (CYP19) activity and endocrine functions. In the present study, 21 organochlorines (OCs) mediated decreases in aromatase activity and protein and DNA content and increases in the percent lactate dehydrogenase (LDH) leakage in JEG-3 cells. These effects were highly variable among the types of OC and their treatment concentrations. Lowest observed effective concentrations reached 0. 001 microM for several OCs. Aromatase activity decreases and OC-mediated cytotoxicity were related. Thus, it was not possible to clearly assess the capacity of the OCs to modulate aromatase activity. Similar to 1,4-naphthoquinone, the most cytotoxic OCs contained a hydroxyl (4'-OH-2,4,6-trichlorobiphenyl and tris(4-chlorophenyl)methanol) or methylsulfonyl- (3- and 4-MeSO(2)-2, 2',5,5'-tetrachlorobiphenyl and -2,3',4',5-tetrachlorobiphenyl, and 3'- and 4'-MeSO(2)-2,2',3,4,5'-pentachlorobiphenyl and -2,2',4,5, 5'-pentachlorobiphenyl) functional group. Modulation of aromatase activity and LDH leakage were less for 3,3',4,4', 5-pentachlorobiphenyl and benzo[a]pyrene and insignificant for five alkyl-substituted trichloro-dibenzofurans and 2,3,7, 8-tetrachloro-dibenzo-p-dioxin (up to 10 microM). Cytotoxicity-related effects were influenced by the cell density and the presence of 10% fetal calf serum in the medium during compound incubation. Similar cytotoxic effects were observed for the JAR cell line. The involvement of an apoptotic mechanism of cytotoxicity in OC-treated JEG-3 cells was suggested by the binding of APO2.7 (an antibody specific to apoptotic cells), DNA fragmentation, and trypan blue staining. JEG-3 and JAR cells appear too sensitive toward OC-mediated cytotoxicity for use as in vitro bioassays to evaluate the potential modulation of aromatase activity. However, these cell lines may prove useful for examining the capacity of xenobiotics to modulate placental toxicity.

Apoptosis↗
PubMed1999

Halogenated environmental contaminants in perch (Perca fluviatilis) from Latvian coastal areas.

The environmental contamination situation in coastal areas of the former Soviet Union has up to now been more or less unknown. This study on perch (Perca fluviatilis), collected at three locations along the coast of Latvia during 1994 and 1995, provides concentrations of several ubiquitous environmental contaminants (PCBs, HCB, HCHs, 4,4'-DDT, 4,4'-DDE, 4,4'-DDD, trans-Nonachlor, 2,2',4,4'-tetrabromodiphenyl ether). The concentrations of total PCB were similar at all study locations [0.7-1.4 ppm on a lipid weight (l.w.) basis], although a site close to the City of Riga indicated the presence of a local PCB contamination source. The contamination source was identified mainly by a higher relative content of lower chlorinated PCB congeners in the samples. Local pollution sources were also indicated for HCH and DDT. A large variation in the HCH isomer composition between 1994 and 1995 at one location demonstrates short half-lives of HCHs in the environment. The brominated flame retardant compound 2,2',4,4'-tetrabromdiphenyl ether was present in the range of 6.4-10 ng/g l.w. in the perch. The clean-up method applied in this study allowed for quantification of two semi-polar contaminants frequently overlooked in Baltic biota, namely Dieldrin and bis(4-chlorophenyl) sulfone (BCPS). Concentrations of BCPS were remarkably high, i.e. in the same magnitude as the most abundant PCB congeners. The results presented shows that the contamination of, e.g. PCB in an area of the former Soviet Union, the Gulf of Riga, is similar to that observed in other parts of the Baltic area.

Animals↗
PubMed1999

Effects of bis(4-chlorophenyl) sulfone on rats following 28-day dietary exposure.

The short-term oral toxicity of a recently identified environmental pollutant, bis(4-chlorophenyl) sulfone (BCPS), was studied. Groups of male Sprague-Dawley rats (n = 6) were administered BCPS via the diet at 0 (control), 10, 100, or 1000 ppm for 4 wk. Additional control and 1000 ppm groups were also treated for 1, 2, and 3 wk. At termination, high-dose animals showed depressed growth rate and food consumption, and 1 high dose animal in each of the wk-1, -3, and -4 groups had marked hematuria. Increased liver to body weight ratio was present at 100 ppm and increased kidney to body weight ratio at 1000 ppm. Marked increases in hepatic benzoylresorufin O-dealkylase (BROD) and pentoxyresorufin O-dealkylase (PROD) activities were detected starting at 10 ppm. There was a significant decrease in methoxyresorufin O-dealkylase (MROD) activity at 1000 ppm. Hepatic UDP-glucuronosyltransferase (UDPGT) and glutathione S-transferase (GST) activities also increased starting at 100 ppm. A marked increase in urinary excretion of ascorbic acid was apparent starting at 10 ppm, while there were no changes in urinary N-acetylglucosaminidase (NAG) activity and protein levels. A threefold increase in serum cholesterol and a 30% increase in platelet counts were observed in the 1000 ppm group. Levels of thiobarbituric acid-reactive substances (TBARS) were increased by threefold in the liver of the high-dose animals but were not significantly altered in the serum. Tissue BCPS concentrations were dose dependent and followed the order: adipose tissue >>> liver > kidneys > brain, spleen, lungs. In the time-course study involving the control and high-dose groups, most of the treatment effects were clearly present in wk 1, and the severity of the effects remained at more or less the same levels thereafter. The exceptions were hepatic BROD and PROD activities, which showed a trend toward further increases with time of treatment. Liver and adipose tissue concentrations of BCPS remained unchanged from wk 1 to wk 4, while kidney concentrations increased with time. The results indicated that BCPS produced hepatic effects at the lowest dose level tested (10 ppm in the diet or 0.8 mg/kg/d).

Administration, Oral↗
PubMed1999

Brominated flame retardants induce intragenic recombination in mammalian cells.

In the present study we have examined the effects of brominated flame retardants (BFR) and several other environmental contaminants in two in vitro assays for intragenic recombination at an endogenous locus in mammalian cells. A total ten compounds were investigated, i. e., two technical PCB mixtures (Aroclor 1221 and Aroclor 1254), DDT, PCP, tetrabromobisphenol A (TBBPA), 4,4'-bischlorophenyl sulfone (BCPS), hexabromocyclododecane (HBCD) and the three different polybrominated diphenylethers (PBDEs): 2-bromodiphenylether (MBDE), 3,4-dibromodiphenylether (DBDE) and 2,4,2', 4'-tetrabromodiphenylether (TBDE). In the SPD8 assay system statistically significant increases in recombination frequency were observed with Aroclor 1221, BCPS, DBDE, DDT, HBCD, MBDE and TBDE. In the Sp5 assay system, only DBDE, HBCD and MBDE caused statistically significant increases in recombination frequency. In conclusion, our findings indicate that the modern additives to plastic, i.e., HBCD and PBDEs, as well as the plastic monomer BCPS may have the same effect to human health as DDT and PCBs, in terms of inducing genetic recombination, which is known to provoke a number of diseases, including cancer.

Animals↗
PubMed1999

Polychlorinated biphenyls and some pesticides in perch (Perca fluviatilis) from inland waters of Latvia.

Polychlorinated biphenyls (PCBs), DDT-related substances, hexachlorocyclohexane (HCH) isomers and hexachlorobenzene (HCB) were analysed in perch (Perca fluviatilis) from Latvian lakes and rivers. DDE is present in the highest concentrations in all samples; 62-170 ng/g lipid weight in perch from rural areas and 460 ng/g in perch from the Riga area. Individual dominating PCB congeners were in the range 16-45 ng/g and 200-210 ng/g, respectively. The degree of contamination of rural areas in Latvia of these organohalogen substances is in the same range as in background areas in Sweden. Riga, the major urban area in Latvia, is shown to be more polluted with PCBs than other areas in Latvia.

Animals↗
PubMed1999

Enlargement of atrophy and visual acuity loss in the geographic atrophy form of age-related macular degeneration.

OBJECTIVE: To describe the progression of geographic atrophy (GA) from age-related macular degeneration (AMD) with respect to visual acuity (VA) loss and enlargement of atrophy. DESIGN: A prospectively observed case series. SETTING: Tertiary retinal referral center. PARTICIPANTS: One hundred twenty-three patients with GA due to AMD who completed at least 1 year of follow-up (median follow-up, 3 years) were examined annually. METHODS: At each examination, a protocol best-corrected VA of each eye was measured, a clinical examination was performed, and color fundus photographs were taken. The areas of atrophy were drawn and measured. MAIN OUTCOME MEASURES: Visual acuity loss and enlargement of total and central atrophy. RESULTS: At baseline, median VA was poorer with larger areas of atrophy, but there was wide variation related to sparing of the fovea. Thirty-one percent of all study eyes suffered a three-line VA loss from baseline by 2 years, and 53% had a three-line loss by 4 years. Those eyes with VA better than 20/50 had the highest rate of acuity loss; 27% of these eyes had acuities of 20/200 or worse at 4 years. Visual acuity loss in the GA study eye was similar in patients with bilateral GA and in those with choroidal neovascularization in the fellow eye. Total atrophy enlarged a median of 1.8 Macular Photocoagulation Study disc areas (DA) at 2 years; atrophy within a 4-DA circle centered on the fovea enlarged a median of 0.9 DA. Two (22%) of nine patients with GA in one eye and only drusen without advanced AMD in the fellow eye developed GA in the fellow eye at 2 years. CONCLUSIONS: Geographic atrophy is associated with a significant decline in VA over time in many eyes. Areas of atrophy continue to enlarge over time, even when already large at baseline. The combination of reduced VA with enlargement of atrophy, occurring bilaterally in most patients, can lead to significant impairment of visual function.

Aged↗
PubMed1999

The use of microsatellite variation to infer population structure and demographic history in a natural model system.

To assess the reliability of genetic markers it is important to compare inferences that are based on them to a priori expectations. In this article we present an analysis of microsatellite variation within and among populations of island foxes (Urocyon littoralis) on California's Channel Islands. We first show that microsatellite variation at a moderate number of loci (19) can provide an essentially perfect description of the boundaries between populations and an accurate representation of their historical relationships. We also show that the pattern of variation across unlinked microsatellite loci can be used to test whether population size has been constant or increasing. Application of these approaches to the island fox system indicates that microsatellite variation may carry considerably more information about population history than is currently being used.

Animals↗
PubMed1999

Localization and comparative toxicity of methylsulfonyl-2,5- and 2,6-dichlorobenzene in the olfactory mucosa of mice.

Several methylsulfonyl (MeSO2) metabolites formed from chlorinated aromatic hydrocarbons have been identified in human milk, lung, and body fat, as well as in the tissues of Baltic grey seals and arctic polar bears. The tissue localization and nasal toxicity of two methylsulfonyl-substituted dichlorobenzenes (diCl-MeSO2-B), with the chlorine atoms in the 2,5-, and 2,6- positions, were investigated in female NMRI and C57B1 mice. Using tape-section autoradiography, animals dosed i.v. with 14C-labeled 2,5-, or 2,6-(diCl-MeSO2-B) showed a preferential uptake of radioactivity in the olfactory mucosa and the tracheobronchial epithelium. Histopathology showed that 2,6-(diCl-MeSO2-B) is a potent toxicant that induces necrosis in the olfactory mucosa following a single dose as low as 4 mg/kg (i.p. injection), whereas 2,5-(diCl-MeSO2-B) induced no signs of toxicity in the olfactory mucosa at doses as high as 130 mg/kg (i.p. injection). Necrosis of the Bowman's glands was the first sign of 2,6-(diCl-MeSO2-B)-induced toxicity followed by degeneration of the neuroepithelium, which implies that the Bowman's gland may be the primary site of toxicity and degeneration of the neuroepithelium may be a secondary effect. Administration of the parent compounds, 1,3-dichlorobenzene and 1,4-dichlorobenzene, or the chlorinated analog 1,2,3-trichlorobenzene (85, 85, and 105 mg/kg, respectively; i.p. injection), induced no signs of toxicity in the olfactory mucosa. These and previous results suggest that 2,6-positioned chlorine atoms and an electron withdrawing substituent in the primary position is an arrangement that predisposes for toxicity in the olfactory mucosa.

Animals↗
PubMed1999

Health condition of the Baltic grey seal (Halichoerus grypus) during two decades. Gynaecological health improvement but increased prevalence of colonic ulcers.

Results obtained at postmortem examinations of 159 Baltic grey seals during the 20-year period 1977-1996 are presented. The investigation was initiated due to a serious reduction of the Baltic grey and ringed seal populations. Earlier, reduced reproductive ability with occlusions and stenoses of the uterus, as well as a disease complex in adult individuals of both sexes, was reported. The disease complex comprised lesions of claws, skull bone, intestine (colonic ulcers), kidneys (glomerulopathy, tubular cell proliferations), arteries (sclerosis) and adrenals (cortical hyperplasia, cortical adenomas). Besides occlusions and stenoses, tumours (leiomyomas) were common in the uterus. This report focuses on the results of a time-trend study covering the two decades 1977-1986 and 1987-1996. The prevalences (%) in the two decades of moderate to severe lesions of claws, intestine, arteries and adrenals are compared, as well as the prevalences of lesions of the female reproductive organs and rate of pregnancy. A similar comparison was made of animals born before 1980 and those born after 1979, in order to investigate a possible relation between the evident decrease in PCB and DDT pollution of the Baltic which occurred in the 1970s and seal health. A positive time trend respecting gynaecological health was confirmed, with a decreased prevalence of uterine obstructions, from 42 to 11%, and an increased prevalence of pregnancies, from 9 to 60%. The high incidence of uterine tumours (leiomyomas) seems to have decreased slowly (from 53 to 43%). Of special interest is the increased prevalence of colonic ulcers in young animals. The findings indicate that the food consumed by the Baltic seals may contain "new" or increased amounts of hitherto unidentified toxic factors which affect their immune system.

Adrenal Cortex↗
PubMed1999

Flame retardant exposure: polybrominated diphenyl ethers in blood from Swedish workers.

Polybrominated diphenyl ethers (PBDEs) are used as additives in polymers and textiles to prohibit the development of fires. Because of the production and use of PBDEs, their lipophilic characteristics, and persistence, these compounds have become ubiquitous environmental contaminants. The aim of the present study was to determine potential exposures of PBDEs to clerks working full-time at computer screens and personnel at an electronics-dismantling plant, with hospital cleaners as a control group. Five PBDE congeners--2,2',4,4'-tetraBDE; 2,2',4,4',5,5'-hexaBDE; 2,2',4,4',5, 6'-hexaBDE; 2,2',3,4,4',5',6-heptaBDE; and decaBDE--were quantified in blood serum from all three categories of workers. Subjects working at the dismantling plant showed significantly higher levels of all PBDE congeners in their serum as compared to the control group. Decabromodiphenyl ether is present in concentrations of 5 pmol/g lipid weight (lw) in the personnel dismantling electronics; these concentrations are comparable to the concentrations of 2,2',4, 4'-tetraBDE. The latter compound was the dominating PBDE congener in the clerks and cleaners. The major compound in personnel at the dismantling plant was 2,2',3,4,4',5',6-heptaBDE. Concentrations of this PBDE congener are almost twice as high as for 2,2',4, 4'-tetraBDE in these workers and seventy times the level of this heptaBDE in cleaners. The total median PBDE concentrations in the serum from workers at the electronics-dismantling plant, clerks, and cleaners were 37, 7.3, and 5.4 pmol/g lw, respectively. The results show that decabromodiphenyl ether is bioavailable and that occupational exposure to PBDEs occurs at the electronics-dismantling plant.

Adult↗
PubMed1998

Actin filaments facilitate insulin activation of the src and collagen homologous/mitogen-activated protein kinase pathway leading to DNA synthesis and c-fos expression.

The exact mechanism of the spatial organization of the insulin signaling pathway leading to nuclear events remains unknown. Here, we investigated the involvement of the actin cytoskeleton in propagation of insulin signaling events leading to DNA synthesis and expression of the immediate early genes c-fos and c-jun in L6 muscle cells. Insulin reorganized the cellular actin network and increased the rate of DNA synthesis and the levels of c-fos mRNA, but not those of c-jun mRNA, in undifferentiated L6 myoblasts. Similarly, insulin markedly elevated the levels of c-fos mRNA but not of c-jun mRNA in differentiated L6 myotubes. Disassembly of the actin filaments by cytochalasin D, latrunculin B, or botulinum C2 toxin significantly inhibited insulin-mediated DNA synthesis in myoblasts and abolished stimulation of c-fos expression by the hormone in myoblasts and myotubes. Actin disassembly abolished insulin-induced phosphorylation and activation of extracellulor signal-regulated kinases, activation of a 65-kda member of the p21-activated kinases, and phosphorylation of p38 mitogen-activated protein kinases but did not prevent activation of phosphatidylinositol 3-kinase and p70(S6k). Under these conditions, insulin-induced Ras activation was also abolished, and Grb2 association with the Src and collogen homologous (Shc) molecule was inhibited without inhibition of the tyrosine phosphorylation of Shc. We conclude that the actin filament network plays an essential role in insulin regulation of Shc-dependent signaling events governing gene expression by facilitating the interaction of Shc with Grb2.

Actin Cytoskeleton↗
PubMed1998

Inhibition of thyroid hormone sulfation by hydroxylated metabolites of polychlorinated biphenyls.

In this study we investigated the possible inhibitory effects of hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) on iodothyronine sulfotransferase activity. The results indicate that OH-PCBs are potent inhibitors of this activity in vitro, with IC50 concentrations in the low micro molar range. Inhibition of sulfotransferase activity towards 3,3'-diiodothyronine (T2) was similar to that towards 3,3',5-triiodothyronine (T3) in this in vitro assay, therefore, T2 can be used as the model substrate for the active hormone T3. An important structural requirement for T2 sulfotransferase inhibition is a hydroxyl group on the para or meta position of the OH-PCBs. Since T3 is the active hormone, playing a very important role in somatic and brain development and since hydroxylated PCBs can accumulate in fetuses, inhibition of T3 sulfation could be a possible mechanism for the developmental neurotoxicity of PCBs.

Animals↗