DiEthylStilbestrol DES, environmental estrogens and obesity
2007 Study Abstract
Dietary substances and xenobiotic compounds with hormone-like activity can disrupt the programming of endocrine signaling pathways that are established during perinatal differentiation. The consequences of this disruption may not be apparent until later in life but increasing evidence implicates developmental exposure to environmental hormone-mimics with a growing list of adverse health effects including reproductive problems and increased cancer risks. Obesity has recently been proposed to be yet another adverse health consequence of exposure to endocrine disrupting substances during development. There is a renewed focus on identifying contributions of environmental factors to the development of obesity since it is reaching worldwide epidemic proportions, and this disease has the potential to overwhelm healthcare systems with associated illnesses such as diabetes and cardiovascular disease. Here, we review the literature that proposes an association of perinatal exposure to endocrine disrupting chemicals, in particular those with estrogenic activity, with the development of obesity later in life. We further describe an animal model of developmental exposure to diethylstilbestrol (DES) to study mechanisms involved in programming for obesity. Our experimental data support the idea that adipocytes and the mechanisms involved in weight homeostasis are novel targets of abnormal programming of environmental estrogens, some of which are found in our foods as naturally occurring substances or inadvertently as contaminants.
Perinatal exposure to environmental estrogens and the development of obesity,Newbold RR1, Padilla-Banks E, Snyder RJ, Jefferson WN, Mol Nutr Food Res. 2007 Jul;51(7):912-7. NCBI PMID: 17604389.
Surgeons could know while their patients are still on the operating table if a tissue is cancerous, according to researchers from the Department of Energy’s Oak Ridge National Laboratory and Brigham and Women’s Hospital/Harvard Medical School.
In the journal Analytical and Bioanalytical Chemistry, a team led by ORNL’s Vilmos Kertesz describes an automated droplet-based surface sampling probe that accomplishes in about 10 minutes what now routinely takes 20 to 30 minutes. Kertesz expects that time to be cut to four to five minutes soon. For this proof-of-concept demonstration, researchers rapidly profiled two hormones from human pituitary tissue.
“Instead of having to cut and mount tissue and wait for a trained pathologist to review the sample under a microscope, a technician might soon perform an equally conclusive test in the operating environment,” Kertesz said.
The new mass spectrometry-based technology provides an attractive alternative to the traditional method called immunohistochemistry, or IHC, which looks for specific protein biomarkers to make a diagnosis. Although the IHC approach provides a high degree of spatial recognition, it is time consuming and limited by the quality and specificity of the antibody used to detect the protein.
ORNL researchers trace this success to patents resulting from previously funded DOE projects and noted that this work advances the liquid microjunction surface sampling probe technology first patented by ORNL. Additionally, ORNL houses the only laboratories in the world that have this automated droplet-based surface sampling probe and the requisite software.
While yet other mass spectrometry-based techniques such as desorption electrospray ionization and rapid evaporative ionization mass spectrometry are being evaluated for classifying tumors and providing prognostic information, they are limited mainly to the analysis of lower molecular weight biomolecules. These include metabolites, fatty acids and lipids. The new droplet-based method developed at ORNL does not share this limitation.
“The ability to quickly characterize the tissue distribution of larger macromolecular biomarkers like peptides and proteins would harness the diagnostic value of validated immunohistochemistry approaches for surgical decision-making,” Kertesz said.
Kertesz noted that this system has been successfully used for spatially resolved sampling and detection of drugs and metabolites from thin sections of animal tissue and proteins from dried blood.
“On the basis of the results and the relative simplicity, rapidity and specificity of our method, there is great potential for our technology to assist surgeons in the detection of cancer from tissue biopsy samples,” said Kertesz, a member of ORNL’s Organic and Biological Mass Spectrometry Group and lead author of the paper – Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC–ESI-MS–MS. Gary Van Berkel of ORNL is a co-author.
MRSA pig superbug found in supermarket raises alarm over farming risks
A special investigation into how the new pig superbug LA-MRSA is spreading onto our plates and into our bodies. Watch the disturbing results of the Guardian’s food tests in four of Britain’s biggest supermarkets, where the superbug has been found in pork. It’s not deadly – but factory pigs overdosing on antibiotics is the latest twist on the long road that, microbiologists warn, will make antibiotics so useless that more of us will be die from antibiotic-resistant drugs than from cancer by 2050.
DDT in Pregnancy May Raise Breast Cancer Rates in Daughters
Women who were exposed to higher levels of the pesticide DDT in utero were nearly four times more likely to be diagnosed with breast cancer as adults than women who were exposed to lower levels before birth, according to a 54-year case-control study.
2015 Study Abstract
Currently no direct evidence links in utero dichlorodiphenyltrichloroethane (DDT) exposure to human breast cancer. However, in utero exposure to another xenoestrogen, diethylstilbestrol, predicts an increased breast cancer risk. If this finding extends to DDT, it could have far-reaching consequences. Many women were heavily exposed in utero during widespread DDT use in the 1960s. They are now reaching the age of heightened breast cancer risk. DDT exposure persists and use continues in Africa and Asia without clear knowledge of the consequences for the next generation.
In utero exposure to DDT is associated with an increased risk of breast cancer.
This was a case-control study nested in a prospective 54-year follow-up of 9300 daughters in the Child Health and Development Studies pregnancy cohort (n = 118 breast cancer cases, diagnosed by age 52 y and 354 controls matched on birth year).
Setting and Participants:
Kaiser Foundation Health Plan members who received obstetric care in Alameda County, California, from 1959 to 1967, and their adult daughters participated in the study.
Main Outcome Measure:
Daughters’ breast cancer diagnosed by age 52 years as of 2012 was measured.
Maternal o,p′-DDT predicted daughters’ breast cancer (odds ratio fourth quartile vs first = 3.7, 95% confidence interval 1.5–9.0). Mothers’ lipids, weight, race, age, and breast cancer history did not explain the findings.
This prospective human study links measured DDT exposure in utero to risk of breast cancer. Experimental studies are essential to confirm results and discover causal mechanisms. Findings support classification of DDT as an endocrine disruptor, a predictor of breast cancer, and a marker of high risk.
Sources and more information
DDT Exposure in Utero and Breast Cancer, The Journal of Clinical Endocrinology & Metabolism, doi/10.1210/jc.2015-1841, June 16, 2015.
Prenatal DDT exposure tied to nearly 4-fold increase in breast cancer risk, THE ENDOCRINE SOCIETY, eurekalert, 16-JUN-2015.
Prenatal DDT exposure linked to increased risk of breast cancer, medicalnewstoday, 17 June 2015.
Startling link between pregnant mother’s exposure to DDT and daughter’s risk of breast cancer, washingtonpost, June 17 2015.
Genital defect in baby boys linked to moms’ chemical exposure
Mothers around a lot of endocrine disrupting chemicals at home or in jobs such as cleaners, hairdressers and laboratory workers during pregnancy are more likely to have baby boys with a genital defect, according to a new study in the south of France.
The study adds to mounting evidence that fetal exposure to chemicals that mimic people’s natural hormones may cause hypospadias, a condition where the opening of the urethra is on the underside of the penis rather than at the tip.
French researchers examined more than 600 children in the south of France and found that babies exposed to endocrine disrupting chemicals while their genitals were developing were more likely to suffer from hypospadias.
Half the boys had hypospadias and half did not. The risk for those exposed was 68 percent higher than the unexposed boys. The researchers ruled out baby boys with known genetic risks for such defects.
“This study is well-crafted and supports the thought that chemicals in the environment are affecting our genital well-being,”
said Dr. George Steinhardt, a pediatric urologist at the Helen DeVos Children’s Hospital in Grand Rapids, Michigan, who was not involved in the study. He added
“This is another little piece of the puzzle that says we are affected by these exposures,”
The defect, which can be minor or quite severe depending on how far the opening is from the tip, can lead to problems with urination and, later in life, sexual difficulty.
About 70 percent of deformities are relatively mild, Steinhardt said.
It is one of the most common genital defects in baby boys, and most cases require surgery, often done before they reach two years old. In the United States, an estimated five out of 1,000 boys are born annually with hypospadias, while Europe’s rate is slightly less than two out of 1,000.
The researchers estimated the unborn babies’ exposure by looking at their parents’ jobs and where they lived. Working with hormone disrupting chemicals and living in homes near heavy polluters were both linked to more baby boys having the defect. However, the researchers did say a limit of the study was attempting to estimate fetal exposure to such chemicals.
Mothers were most likely to have boys with hypospadias if they worked as a cleaner, hairdresser or beautician.
Some of the endocrine disrupting chemicals linked to the professions involved in the study were bisphenol-A (BPA), phthalates, polychlorinated compounds, alkylphenolic compounds and organic solvents.
Most exposures—78 percent—occurred in the window of development when babies’ genitals are forming.
“We found that fetal exposure to [endocrine disrupting chemicals] was a significant risk factor for hypospadias in our series. The types of substance having an impact on the phenotype were heterogeneous, but detergents, pesticides, and cosmetics accounted for 75 percent of the cases,”
the authors wrote in the study published in the European Urology journal this month.
The authors were not available for an interview.
The study doesn’t prove that the exposure caused hypospadias, as chemical exposure isn’t the only possible cause. However, it is plausible since such chemicals impact the developing endocrine system,
said Dr. Laurence Baskin, professor of urology and chief of pediatric urology at University of California, San Francisco, who added that it would be most likely due to a disruption in the boys’ androgen hormones while their penis was developing.
Other possible causes of the birth defect include older, obese mothers, and fertility or hormone treatments during pregnancy, according to the U.S. Centers for Disease Control and Prevention.
In reviewing potential causes of hypospadias, European and Australian pediatric researchers found that “having an affected family member is the highest identified risk factor so far.” In the European and Australian researchers’ report, which examined recent science of hypospadias causes, they also concluded that mothers’ chemical exposure might also cause the defects or raise the risk for those boys already predisposed through their genes.
One of the major strengths of the current study was the exclusion of a lot of children with known genetic risk factors for hypospadias, Baskin said.
“It’s an outstanding study with both age and culturally matched children,”
This wasn’t the first time scientists have found a link between certain chemicals and hypospadias. Mothers in southeast England who were heavily exposed to endocrine disrupting phthalates on the job were about three times as likely to have a baby boy with hypospadias. Phthalates are used in some cosmetics, fragrances, food packaging and PVC plastics.
In 2010, Italian researchers found that among 160 mothers, those who worked with more than one group of endocrine disrupting chemicals were four times as likely to have a baby boy with hypospadias.
Baskin said the French study could help stem hypospadias prevalence. He added :
“Nobody dies from hypospadias, most are cured with surgery, but if we can come up with some kind of prevention protocol, it could prevent a lot of surgeries and anxiety for families,”
For questions or feedback about this piece, contact Brian Bienkowski.
Cervical cancer is not just a young woman’s disease…
Cervical screening programmes in many countries stop at around the age of 65 and much of the focus is often on younger women. For example, recent media campaigns in England and Wales have centred on lowering the age at first screening. Comparatively little attention has been given to older women despite the fact that they account for about a fifth of cases each year and half of deaths. Of the 3121 women diagnosed on average each year between 2009 and 2011 in the UK, only 64 were younger than 25 compared with 616 who were older than 65. As the population ages, this number of older women affected is set to increase. Susan Sherman and colleagues argue that screening programmes should reflect this.
Sources and more information
Cervical cancer is not just a young woman’s disease, BMJ 2015;350:h2729, 15 June 2015.
Review calls for urgent change to perception of cervical cancer risk in older women, Keele University, 15 June 2015 .
Cervical cancer screening: review calls for urgent screening changes, medicalnewstoday, 16 June 2015.
Rencontre avec Irène Frachon, qui a publié son récit Mediator 150 mg, sous-titre censuré, chez editions-dialogues, où elle raconte comment elle a fait interdire ce médicament à la vente en France. Réalisation : Ronan Loup.
En savoir plus
Irène Frachon : «Je crois aux mouvements de contre-lobby», lemonde, 15.06.2015.