Plastic and Cancer

Introduction:

Plastic is ubiquitous in our lives because it is convenient and relatively inexpensive.  It is convenience comes from being lightweight and its ability to absorb impact shock without breaking, which on its own merit, is hard to argue with.  Plastics are so versatile in use that their impacts on the environment are extremely wide ranging, posing serious challenge for disposal.  Although plastic is convienent in our everyday lives, it can pose serious health effects due to the chemicals it contains.

The next few sections will explain what the compound BPA is, the history of the compound and how it correlates with different types of Cancer.

BPA is a chemical building block used primarily in polycarbonate plastics and the epoxy linings of metal and possibly from dental sealants. BPA is classified as an Endrocrine Disrupter.  Endocrine disrupters are compounds that mimic normal actions of all endocrine hormones including estrogens, androgens, thyroid, hypothalamic and pituitary hormones.

Types of endocrine disrupters

 

 

 

 

 

 

 

Chemical Structure of BPA:

C15H16O2 or (CH3)2C(C6H4OH)2

Bisphenol A

Characteristics:

  • 4,4′-dihydroxy-2,2-diphenylpropane
  • BPA, 4,4′-(propan-2-ylidene)diphenol,
  • p, p’-isopropylidenebisphenol, 4,4´-isopropylidenediphenol.
  • Molecular formula C15H16O2
  • Molar mass 228.29 g mol−1
  • Appearance White to light brown flakes or powder
  • Density 1.20 g/cm³, solid
  • Melting point  158 to 159 °C (430 K)
  • Boiling point 220 °C (493 K) / 4 mmHg
  • Solubility in water 120–300 ppm (at 21.5 °C)

Bpa molecules are bound by ester bonds to form a polymer used to make polycarbonate plastics. These bonds are consdiered to be unstable and the use of heat, acids and bases can disrupt this bond leaching BPA into foods and liquids.

Examples of man made EDC’s are considered more harmful than naturally occurring EDC’s and are: lame-retardant polybrominated diphenyl ether (PBDE), diethylstilbestrol (the drug DES), the plasticizer bisphenol A (BPA), heavy metals, solvents, pesticides [such as organophosphates, dichloro-diphenyl-trichloroethane (DDT)], phthalates, dioxins, polychlorinated biphenyls (PCBs), and butyltins.  Although these compounds are not necessarily potent on their own merit, they often times work together to form a stronger more potent chemical product.

EDC’s Modes of Action:

  • Binding to Nuclear Receptors such as the estrogen Receptor
  • Nuclear receptor Antagonist
  • Activating expression of P450 enzymes

History:

1891-BPA invented in a laboratory.

1938– Dodds found that BPA was an artificial estrogen.  Researchers found that BPA had similar toxic effects to DES-a drug taken off the market due to findings that it caused reproductive cancers in girls whose mother’s had taken DES during pregnancy.

1940’s and 50’s-BPA is used in plastics such as polycarbonate and epoxy.  These are found in baby bottles, metal food cans, water bottles, water coolers and many more.  There are no regulations in place for the amounts used in the production of these products.

1976 the first law to regulate chemicals and their toxicity came into play.  However BPA was not considered to be a toxic chemical.

1988-According to the EPA a “safe” amount of BPA was calculated at  50 micrograms per kilogram of body weight per day (50 ug/kg/d). However many studies were done to show that BPA was harmful at levels much lower than this standard.   There was no change of governmental regulation at this time regardless of the evidence.

1996-first FDA assessment of the Drug proved that levels found were still considered “safe”.

1997-Fred Vom Saal from the University of Missouri-Columbia found that low levels of BPA had a harmful effect on the prostate and that the EPA’s level of “safe” exposure was much too high and inaccurate.  See (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC20042/?tool=pubmed)  Studies over the next generation proved that low doses of BPA were linked to breast cancer, prostate damage, early puberty, and behavioral problems.

2003-2006 First Serious Government Assessment of BPA-controversial assessment due to biases and special interests.

June 2007 -Study linking BPA to diabetes and heart disease.  “BPA mimics estrogen, and high levels of estrogen in the body increases the body’s sugar production, which can lead to diabetes and heart disease”.

2007-Group of Independent BPA researchers collectively known as the Chapel Hill Panel conclude that amounts of BPA present a clear risk to human health.  Many studies were run on baby bottles and showed that 1 in 16 babies are exposed to amounts of BPA that were toxic in their animal case studies.

2008-Studies are done to show that BPA leaches into baby bottles from heating materials in plastic.

2008 Congress demanded that the FDA prove that levels of BPA were safe

Spring 2008-Government finds that levels of BPA pose a risk to humans and certain retail stores such as Wal-Mart and Toys R Us pull BPA made products off their shelves.  http://cerhr.niehs.nih.gov/chemicals/bisphenol/BPADraftBriefVF_04_14_08.pd

Summer 2008 FDA again concludes that BPA levels are”safe” and there is another controversial issue that arises due to an FDA member being paid by a manufacturer.

Connecticut, New Jersey, and Delaware urge 11 baby bottle manufacturers to stop using BPA.

2009-20 states Introduce a bill to reduce levels of BPA exposed to children

January 2010 FDA admits a slight concern for BPA

2010-10 more states introduce bills on BPA

Currently Canada has an entire ban on substances made with BPA and they feel the costs are much less than the health of children.

Denmark has also banned the use of BPA in the production of infant food products and continues to urge other countries to do the same.

2010-EPA devises plan to reduce risks of BPA

May 25, 2010: President’s Cancer Panel warns of Toxic Effects ofBPA

Japan: manufacturers switched to an ethylene lining for canned foods to avoid BPA contamination

Implications:

BPA in Fetuses: Researchers say young children and fetuses especially are extremely vulnerable to toxic effects of BPA.  Tests have been performed to test the levels of BPA in fetuses as well as in break milk.  The fact that researchers were able to find it in breast milk may answer some questions regarding the effect of BPA on breast cancer.  Early exposure to BPA may have many multiple developmental effects.  Recent animal studies have shown that even low dose exposure levels alter the development of the mammy gland in ways that predispose the animal to cancer later on in life.  This may also induce early puberty.  Click here to see a chart to show the critical stages of development due to endocrine disrupters.

Breast Cancer: A recent Yale study found that exposure of BPA to pregnant mice produced an increased ammount of EZH2 in their offspring.  Higher levels of this protein in humans has been linked to an increased risk of breast cancer.  It may also may lead to reproductive tract disorders in women

Obesity: Some research has shown that endocrine disruptors play a role in childhood obesity.  Particularly because of the lipophilic attribute.  Theses EDC’s can be stored in the body as fats and even transfered into the fetus via the placenta.  Studies in mice have shown that BPA triggers 3T3-L1 cells to differentiate into adipocytes and if BPA is taken with insulin, this rate is increased.

Neurological: A recent study at Yale University also found that there is a link between BPA and the neurological system.  Researchers tested monkeys with the amount of BPA that is considered “safe” according to the EPA. Results showed an abundance of mood disorders as well as irregular brain function.  Click here to see chart of different stages of development and effects of endrocrine disrupters

Prostate Cancer: BPA is a possible predisposing factor for prostate cancer.  Studies have shown that prenatal exposure to BPA may cause prostate cancer.  A rat study done at the University of Illinois at Chicago provided evidence of low dose amounts of BPA during development linking to prostate cancer later on in life.

Heart Disease and Diabetes: A study was done by Lang et al. and published in the Journal of the American Medical Association on September 16th, 2008 that suggested a link between raised levels of urinary BPA to increased occurrence of serious medical conditions, including heart disease and diabetes.

Plastic and Health Effects:

Plastic Common Uses Adverse Health Effects
Polyvinyl
chloride
(#3PVC)
Food packaging, plastic wrap, containers for toiletries, cosmetics, crib bumpers, floor tiles, pacifiers, shower curtains, toys, water pipes, garden hoses, auto upholstery, inflatable swimming pools Can cause cancer, birth defects, genetic changes, chronic bronchitis, ulcers, skin diseases, deafness, vision failure, indigestion, and liver dysfunction
Phthalates
(DEHP,
DINP,
and others)
Softened vinyl products manufactured with phthalates include vinyl clothing, emulsion paint, footwear, printing inks, non-mouthing toys and children’s products, product packaging and food wrap, vinyl flooring, blood bags and tubing, IV containers and components, surgical gloves, breathing tubes, general purpose labware, inhalation masks, many other medical devices Endocrine disruption, linked to asthma, developmental and reporoductive effects. Medical waste with PVC and pthalates is regularly incinerated causing public health effects from the relese of dioxins and mercury, including cancer, birth defects, hormonal changes, declining sperm counts, infertility, endometriosis, and immune system impairment.
Polycarbonate, with Bisphenol A (#7) Water bottles Scientists  have linked very low doses of bisphenol A exposure to cancers, impaired  immune function, early onset of puberty, obesity, diabetes, and  hyperactivity, among other problems (Environment California)
Polystyrene Many food containers for meats, fish, cheeses, yogurt, foam and clear clamshell containers, foam and rigid plates, clear bakery containers, packaging “peanuts”, foam packaging, audio cassette housings, CD cases, disposable cutlery, building insulation, flotation devices, ice buckets, wall tile, paints, serving trays, throw-away hot drink cups, toys Can irritate eyes, nose and throat and can cause dizziness and unconsciousness. Migrates into food and stores in body fat. Elevated rates of lymphatic and hematopoietic cancers for workers.
Polyethelyne
(#1 PET)
Water and soda bottles, carpet fiber, chewing gum, coffee stirrers, drinking glasses, food containers and wrappers, heat-sealed plastic packaging, kitchenware, plastic bags, squeeze bottles, toys Suspected human carcinogen
Polyester Bedding, clothing, disposable diapers, food packaging, tampons, upholstery Can cause eye and respiratory-tract irritation and acute skin rashes
Urea-
formaldehyde
Particle board, plywood, building insulation, fabric finishes Formaldehyde is a suspected carcinogen and has been shown to cause birth defects and genetic changes. Inhaling formaldehyde can cause cough, swelling of the throat, watery eyes, breathing problems, headaches, rashes, tiredness
Polyurethane
Foam
Cushions, mattresses, pillows Bronchitis, coughing, skin and eye problems. Can release toluene diisocyanate which can produce severe lung problems
Acrylic Clothing, blankets, carpets made from acrylic fibers, adhesives, contact lenses, dentures, floor waxes, food preparation equipment, disposable diapers, sanitary napkins, paints Can cause breathing difficulties, vomiting, diarrhea, nausea, weakness, headache and fatigue
Tetrafluoro-
ethelyne
Non-stick coating on cookware, clothes irons, ironing board covers, plumbing and tools Can irritate eyes, nose and throat and can cause breathing difficulties

Recommendations to avoid BPA:

  • Buy food in glass or metal containers; avoid polycarbonate drinking bottles with Bisphenol A
  • Avoid heating food in plastic containers, or storing fatty foods in plastic containers or plastic wrap.
  • Do not give young children plastic teethers or toys
  • Use natural fiber clothing, bedding and furniture
  • Avoid all PVC and Styrene products

Resources:

http://www.ewg.org/reports/bpatimeline

http://www.environmentcalifornia.org/environmental-health/stop-toxic-toys/bisphenol-a-overview

ww.bpa.org

http://www.breastcancerfund.org/clear-science/chemicals-glossary/bisphenol-a.html

http://www.foodconsumer.org/newsite/5/bpa_des_may_boost_breast_cancer_2905101057.htm

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2566897/?tool=pmcentrez

http://www.huffingtonpost.com/samuel-s-epstein/presidents-cancer-panel-w_b_566541.html

http://www.ewg.org/node/27511

http://www.naturalnews.com/025801_BPA_plastics_health.html

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570083/

http://www.efsa.europa.eu/en/ceftopics/topic/bisphenol.htm

http://www.google.com/search?client=safari&rls=en&q=endocrine+disrupters+picture&ie=UTF-8&oe=UTF-8XX

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Breast Cancer Lecture

Everyone knows someone who has been affected by Cancer. And so the second half of today’s lecture dealt with one of the most common types; Breast Cancer.

Dennis Ryan - www.pinnkribbonlabels.com

We started off by discussing the basic structures associated with Breast tissue.  Below is  a picture of the cross section of breast tissue:

1) Rib 2) muscle tissue 3) lobule 4) Nipple 6) Duct 7) Adipose Tissue

Although there are many types of breast cancer these are the four basic and common types.

  1. Ductal Carcinoma In situ
  2. Lobular Carcinoma in Situ
  3. Invasive Ductal Carcinoma
  4. Invasive Lobular Carcinoma

1-Ductus Carcinoma In Situ:


This is a disease of the ducts and is still considered a cancer even though it does not invade the basal membrane. ( In situ means still within the duct.)
There are 2 grades of DCIS-Low grade and High grade.

Low

a) Solid form-hyper proliferation of epithelial cells

b) Papillary form-you will see fingerlike projections in the lumen

c) Cribriform-large pieces of hole sections resembling swiss cheese


High-Here you can see a nicrotic center-(cells in the middle are dead or dying). In this case there is no movement of nutrients in or out of cell due to this nicrotic center.

2) Lobular Carcinoma In Situ-Again, this is not an invasion of the basement membrane however this one is not classified as cancer.  The important information about lobular carcinoma in situ is that has high risk to progress into cancer.

3) Invasive Ductal Carcinoma-This is the state at which the actual invasion of the basal membrane begins.

4) Invasive Lobular Carcinoma-Here you can see the indian file migration of cells outside the basement membrane

.

Risk Factors:

There are many risk factors that correlate and can trigger mutations.  Gender is the #1 risk factor due to an increase in female breast tissue as well as exposure to estrogen.

Exam Question: Case study-Perform Risk Analysis

  • Increasing Age-more exposure to estrogen
  • Family History and Personal History
  • Having one first degree relative increases your risk, and having 2 first degree relatives increases your risk 5 fold. Also already having breast cancer increases the chances by 3-4x.
  • Race/ethnicity-Asian, Hispanic and Native American woman have a low risk of developing and dying from breast cancer.  White women are most at risk of developing breast cancer although African American woman are more likely to die of breast cancer.
  • Tissue Architecture-Woman with larger more dense breasts have an increased risk due to more ductal and lobular tissue.
  • # of Menstrual cycles- <12 years old or >55 increases risk
  • Radiation to the chest-slight increase in risk due to radiation exposure
  • Childbirth-This reduces the risk of breast cancer because you do not menstrate during this time period and therefore are exposed to less estrogen. However having a child after age 30 has shown to have a correlation with increased risk.
  • Breast Feeding-slightly decreases risk especially for woman who breast feed for up to 2 years.
  • Oral Contraceptives-slight increase in risk associated with oral contraceptives although if they have not been taken for >10 years the risk goes back to normal levels.
  • Hormone Replacement Therapies-2 types-PHT and ERT.  PHT is prescribed to those women who still have a uterus.  PHT is used because it contains estrogen and progesterone to offset possible development of uterine cancer.  ERT is prescribed for those who have had a hysterectomy and no longer need progesterone.  It has been shown that using PHT does increase the risk of developing and dying from cancer.  ERT does not show and increased risk unless used for more than 10 years.
  • Alcohol Consumption-if used in excess may cause an increase in probabililty  http://www.webmd.com/breast-cancer/guide/20061101/alcohol-breast-cancer-risk
  • Obesity-obesity is especially correlated with women (or men) that gain weight at a later age.  Adipose tissue produces estrogen and increases risk.
  • Exercise/Lifestyle-The more active the less adipose tissue
  • Diet-diets high in fat are not clearly linked to breast cancer however again more adipose tissue correlates with an increase in estrogen.
  • Anti-Perspirant-very weak link between using deodorant and increasing your chances of developing breast cancer.
  • Bras-Weak link between wearing bras and increasing your possibility.
  • Tobacco Smoke-there has not been conclusive evidence in this debate however smoking does correlate with many other cancer types.
  • Breast Implants-the only evidence in this situation is the fact that breast implants make it harder to see developing tissue in mammograms
  • Night Shift work-increased risk due to lower levels of melanin
  • Estrogen Mimics-theses are compounds found in the environment (BPA) such as my large pink plastic water bottle.  These compounds mimic estrogen and therefore may increase risk.

After talking about the risk factors we also talked about some of the beneficial effects of estrogen.  Many of the drugs manufactured today mimic the chemical structure of estrogen and therefore can bind with the estrogen receptor. One of the most common drugs is called Tamoxifen.  This drug acts as an antagonist to estrogen by binding to the estrogen receptor and not allowing the estrogen receptor to activate gene expression. So therefore you are switching off the effects of estrogen.

This video talked about the correlation of exercise (yoga) with a new drug evista and talked about the side effects being less invasive than even Tamoxifen.

GENETICS:

Only 5-10% of breast cancers are traced back to a genetic link.  However, when this occurs there tends to be a mutagen to the BRCA1 and BRCA2 genes.  These genes typically produce proteins that keep cells from abnormal growth however when they are genetical predisposed to contain a mutation, the chances of developing breast cancer increases significantly.  We talked about double stranded breaks in DNA and how BRCA usually binds to these breaks to  facilitate the repair.  However, if BRCA has been mutated than non-homologous end joining occurs.  This process increases rates of errors and therefore mutations

Mutations to Genes ATM, P10 CHEK2 CDH1 and P53 also increase chances of developing breast cancer.  However these mutation are much more rare.

After discussing the risk factors in short detail we broke into groups of 4 and began our Risk analysis on 4 different Case studies.  Many of these factors above were used in our analysis.

Breast Cancer Walks in Denver 2010 Summer and Fall:

  • Sunday October 3rd at the Pepsi Center-Komen Denver Race for the Cure
  • Avon Walk Rocky Mountains June 26th-27th
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