Disease relevance of DDE

• METHODS: We measured plasma levels of DDE and PCBs prospectively among 240 women who gave a blood sample in 1989 or 1990 and who were subsequently given a diagnosis of breast cancer before June 1, 1992 [1].
• Our aim was to investigate the association between DDE exposure and preterm birth [2].
• In addition, adrenocortical adenomas, spontaneous to Syrian golden hamsters, were more frequent in DDE- and DDT-treated animals than in control animals [3].
• In addition, we show that the lack of DDE-type integrase genes from elements of the DIRS1 group is explained by the finding that the previously uncharacterized ORFs of these elements encode proteins related to the site-specific recombinase of bacteriophage lambda [4].
• Liver cancer mortality increased significantly with adipose DDE levels in both sexes among whites, but not among African Americans [5].

Psychiatry related information on DDE

• Objective: To determine whether exposure to polychlorinated biphenyls (PCBs) or dichlorodiphenyl dichloroethene (DDE), either transplacentally or through breast feeding, affected scores on the Bayley Scales of Infant Development at 6 or 12 months of age [6].
• These findings suggest that PCB/DDE exposure from Great Lakes fish has not significantly impaired hand steadiness or visual-motor coordination in this sample of older adults [7].
• Nineteen 9-week-old brown pelicans (Pelecanus occidentalis), obtained from a colony in Vero Beach, Florida, containing environmentally acquired p,p'-DDE residues, were subjected to a food deprivation experiment [8].
• The odds ratio of breast cancer, adjusted for age and centre, for the highest versus the lowest fourth of DDE distribution was 0.73 (95% confidence interval 0.44 to 1.21) and decreased to 0.48 (0.25 to 0.95; P for trend = 0.02) after adjustment for body mass index, age at first birth, and current alcohol drinking [9].
• Although the difference of AhRag between European and Inuit men could not be explained by CB-153 or p,p'-DDE levels alone, we believe that the variation of AhR serum activity reflects different pattern of POP exposure, genetics and/or life style factors [10].

High impact information on DDE

• Several studies have reported higher blood levels of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and polychlorinated biphenyls (PCBs) in patients with breast cancer than in controls [1].
• Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist [11].
• DDT is reductively dechlorinated to DDD and dehydrochlorinated to DDE; it has been thought that DDE is not degraded further in the environment [12].
• Residues of DDE in addled eggs showed a significant inverse relation, confirming the effects of this toxicant on bald eagle reproduction at the population level and the effectiveness of the ban on DDT [13].
• This active site uses all three DDE residues from the subunit bound to the transposase binding site proximal to the cleavage site on the other Mu DNA end (catalysis in trans) [14].

Chemical compound and disease context of DDE

• We measured plasma levels of 2,2-bis(p-chlorophenyl)ethylene (DDE), the major metabolite of DDT, and PCBs prospectively, comparing women who were diagnosed with breast cancer between 1 month and 4 years after blood collection with control women in whom breast cancer did not develop [15].
• A nested case-control study was conducted to examine the association between serum concentrations of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), the primary metabolite of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), and polychlorinated biphenyls (PCBs) and the development of breast cancer up to 20 years later [16].
• The RR of otitis media over the entire first year of life also increased with prenatal exposure to p,p'-DDE (RR, 1.52; CI, 1.05-2.22) and hexachlorobenzene (RR, 1.49; CI, 1.10-2.03) [17].
• Neurosteroid-induced hyperalgesia through a histamine release is inhibited by progesterone and p,p'-DDE, an endocrine disrupting chemical [18].
• After adjusting for maternal race, triglyceride level, and cholesterol level, compared with boys whose mothers had serum DDE levels < 27.0 ng/mL, boys whose mothers had serum DDE levels > or = 61.0 ng/mL had odds ratios of 1.34 [95% confidence interval (CI), 0.51-3.48] for cryptorchidism and 1.18 (95% CI, 0.46-3.02) for hypospadias [19].

Biological context of DDE

• To elucidate the organization of active sites within this tetramer, the subunit providing the essential active site DDE residues for each cleavage and joining reaction was determined [14].
• The finding that serum DDE levels increase with age suggests that no equilibrium in body burden has been reached or that pharmacokinetics or serum/adipose partition may vary with age [20].
• After adjustment for first-degree family history of breast cancer, lifetime lactation, and age at first full-term pregnancy, conditional logistic regression analysis showed a fourfold increase in relative risk of breast cancer for an elevation of serum DDE concentrations from 2.0 ng/mL (10th percentile) to 19.1 ng/mL (90th percentile) [21].
• A mutation in a DDE motif abolishes both endonucleolytic and phosphoryl transfer activities, suggesting that Tc1A carries a catalytic core common to retroviral integrases and IS transposases [22].
• When one of the hyperactive Tnps is replaced with a catalytically inactive version containing the mutation EA326 (DDE mutant), the predominant reaction product is a linearized plasmid resulting from single end cleavage [23].

Anatomical context of DDE

• DDE-induced egg-shell thinning in birds has caused severe population declines in a number of raptor species in Europe and North America. Endocrine-disrupting chemicals have adversely affected a variety of fish species [24].
• The urine, feces and liver were analyzed and in all cases most of the radioactivity observed was identified as unchanged DDE [25].
• The ratios of the sum of MeSO2-DDEs to p,p'-DDE were 1/455 and 1/61 in adipose tissue and liver, respectively, calculated from the median values [26].
• Methylsulfonyl metabolites of PCBs and DDE in human milk in Sweden, 1972-1992 [27].
• The authors measured polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in maternal serum, cord blood, placenta, and serial samples of breast milk from 868 women [28].

Associations of DDE with other chemical compounds

• Laboratory experiments with DDE-containing marine sediments showed that DDE is dechlorinated to DDMU in both methanogenic and sulfidogenic microcosms and that DDD is dehydrochlorinated to DDMU three orders of magnitude more slowly [12].
• A specific association was observed between a glycine to valine substitution at codon 12 and both p,p'-DDT and p,p'-DDE concentrations (odds ratio 15.9, p=0.044 and odds ratio 24.1, p=0.028; respectively) [29].
• Nuclear accumulation of CAR, but not PXR, was observed in the liver tissue following DDE and PB treatment [30].
• This procedure was designed primarily to protect piscivorous birds and mammals from compounds that bioaccumulate in fish and was used in the Great Lakes Water Quality Initiative (GLI) to calculate wildlife values (WV) for mercury, DDT/DDE, total polychlorinated biphenyls (PCBs), and 2,3,7,8-tetrachlorodibenzodioxin (TCDD) [31].
• In our previous study we have shown that a water-soluble derivatized dextran named DDE, containing 82.2% methyl carboxylic acid groups, 6.1% benzylamide, and 5.6% sulfonate with a specific anticoagulant activity equivalent to heparin of 0.5 IU/mg could potentiate the mitogenic activity of aFGF on CCL39 cells [32].

Gene context of DDE

• Androgen receptor activities of p,p'-DDE, fenvalerate and phoxim detected by androgen receptor reporter gene assay [33].
• Linear-regression analysis showed that interleukin-4 (IL-4) plasma levels were associated with plasma levels of DDT 4.4 (p = .0001) and DDE 4.4 (p = .001) [34].
• These results suggest that p,p'-DDT and o,p'-DDT exerted their effects on neuronal cells by the stimulation of p44/42 MAPK, and p,p'-DDE had less effects than the other two organochlorines [35].
• Furthermore, the critical DDE catalytic triad of RAG1 is shared with the Transib transposase as part of conserved motifs [36].
• In this report, p,p'-DDE, a weak androgen receptor (AR) antagonist, has been examined in a Tier I screening battery designed to detect endocrine-active compounds (EACs) [37].

Analytical, diagnostic and therapeutic context of DDE

• DDE and PCBs were measured by gas chromatography in the sera of 58 women with a diagnosis of breast cancer 1-6 months after they entered the cohort and in 171 matched control subjects from the same study population who did not develop cancer [21].
• The authors used stored serum samples to examine the relation between maternal DDE levels during pregnancy and adjusted odds of cryptorchidism (n = 219), hypospadias (n = 199), and polythelia (extra nipples) (n = 167) among male offspring, using a nested case-control design with one control group (n = 552) [38].
• In this case-control study, we examined the effect of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), hexachlorobenzene (HCB), mirex, and several measures of polychlorinated biphenyls (PCBs) on postmenopausal breast cancer risk [39].
• In control patients, DDE and PCB half-lives were strongly correlated (r(s) = 0.71), and the half-life of DDE (but not that of PCB) was inversely correlated with body mass index (BMI), yet the blood serum levels of PCB (but not those of DDE) were correlated with BMI [40].
• METHODS: We conducted a cross-sectional study of semen quality and serum concentration of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) among 763 men [41].

References