. Environmental Oncology - PowerPoint Presentation

1. .Environmental OncologyAs our understanding of science and health expands, our conceptions change as well.

2. Final Project Deadlines & GuidelinesFor the presentation, use PowerPoint slides or scientific posters; accommodations can be made; you will present during the last lab. No excuses.You must post a pdf or ppt of your presentation, if you are using the overhead, on Blackboard before the start of class – go to Discussions, Final Presentations, Create ThreadA hard copy of your paper is due at the start of the last day of class – no excuses. No direct quotes are allowed – each quote will reduce grade by ten pointsAs with homework, any paper with plagiarized material will not be accepted and student will receive a zero. Proper documentation using APA format and a bibliography with a minimum of three peer-reviewed sources from academic or scientific journals are required

3. Final Paper Rubric3 points2 points1 point0 pointsFormatCoversheet. Labeled: Introduction; Methods/Materials; Results; Conclusion; ReferencesCoversheet, labeled 3-4 of the sections; or no coversheet and 5 labels.Labeled 2-1 of the sections; no coversheet, abstract but 3-4 labelsLabeled none, no format. IntroThoroughly described background research of toxin, health risks, ecosystems; 1 page minimumLess than 1 page but accurate, descriptive; or 1 page but not thorough or incorrectDid not describe background research acceptably, less than 1 pageNo introductionMethods/ MaterialsDescribed methods thoroughly and precisely; easy to read and replicateWas not thorough or precise in description of methods – forgot details such as specific unitsResearch methods were not easy to read and would not be replicable No research methods sectionResultsShows results clearly and accurately in bar charts, and describes results clearly and accurately in paragraph formGraphs but inaccurate/ incomplete descriptions or vice versa (descriptions but inaccurate/incomplete graphs)Had either graphs or written descriptionsNo ResultsConclusionDemonstrates understanding of research, analyzes data with insight and objectivity; discusses Shows some understanding, analysis and application is there but lacking in depthShows little understanding, application or analysisNo Conclusion sectionReferencesUsed a minimum of 3 peer-reviewed sources, properly formatted in APA Used 2 peer-reviewed formatted references; or 3+ unformatted sourcesUsed 1 peer-reviewed, formatted reference or 2 peer-reviewed, unformattedNo references or 1+ unformatted source

4. Cancer and our EnvironmentOnco: Greek onkos, “mass”; cancer forms tumorous masses of cellsOncology: study of cancerEnvironmental oncology: study of how environmental factors affect the development of cancerCancer is caused by changes (mutations) in a cell's DNA Some of these changes may be inherited from our parents, while others may be caused by outside exposures: environmental factors. Environmental factors can include: lifestyle (nutrition, tobacco use, physical activity, etc.)Naturally-occurring exposures (ultraviolet light/sunlight, radon gas, viruses/infectious agents, etc.)medical treatments (chemotherapy, radiation, immuno-suppressant drugs)workplace and household exposures (asbestos, pesticides, etc.)pollution

5. CarcinogenesisCancer (“onco”) involves a series of mutationsProto-oncogenes: Stimulate mitosis; become oncogenesTumor suppressor genes: Inhibit mitosis; prevent uncontrolled cell growth: cancers appear when the suppressors do not function.Malignant tumors start by a gradual accumulation of mutations:Convert proto-oncogenes to oncogenes Knock out tumor-suppressor genes Mutations in oncogenes and tumor suppressorgenes:Stimulate mitosis uncontrollablyLead to tumor formation

6. Sources of Environmental Exposure to CarcinogensMicro-environmentHomes (indoor air, consumer products)LifestylePersonal care productsFoodMacro-environmentFarming (factory farms vs mid-sized organic)GMOIndustrial pollutionAir/WaterRegulatory climate/chemicals policy

7. Indoor Air PollutantsAmericans spend 90% of their time indoorsDozens of Indoor Air Pollutants – some are carcinogenicVolatile Organic Chemicals (paint, furniture, wall board, dry cleaning fluid)Contaminants in dust (lead, asbestos, flame retardants, phthalates)Combustion contaminants (natural gas, kerosene) like carbon monoxidePerchloroethylene (dry cleaning fluid)Pesticides, including banned onesCigarette smokeRadon

8. TumorsTumors: abnormal growth of cellsBenign tumors are not cancerousDo not invade neighboring tissue or spreadMalignant tumors are cancerousReadily invade neighboring tissuesThey metastasize: they may also detach and lodge in distant placesResults from mutation of genes regulating the cell cycleCarcinogenesis: development of cancerTends to be gradualMay be years before a cell is obviously cancerous (that is, abnormal DNA and are dividing and growing out of control at a rate to form tumors)Tumors from a patient who had liver cancer

9. Characteristics of Cancer CellsLack differentiation – normal cells have very distinct characteristics depending on their functionAre non-specialized (non-specific to an organ or tissue – hence a breast cancer cell can become a brain cancer cell)Are virtually immortal (can enter the cell cycle repeatedly)Have abnormal nucleiMay be enlargedMay have abnormal number of chromosomesMay have extra copies of genesCancer cells Muscle cellsFat cells

10. Cancer Cell Characteristics cont.Form tumors – masses of cells in an areaCell division is usually controlled by contact with neighboring cells, AKA, contact inhibitionNormal cells will stop replicating when there are too many cells in the area – when they feel other cells in close contact, they stop replicating so that the area doesn’t get too crowdedCancer cells have lost contact inhibition, therefore keep growing and dividing

11. Characteristics of Cancer Cells cont.Undergo metastasis: the process by which cancer spreads from the place at which it first arose as a primary tumor to distant locations in the bodyOriginal tumor splits apart, cells move through the bodyNew tumors appear in other organsUndergo angiogenesis: The process of developing new blood vesselsBrings nutrients and oxygen to the tumor

12. Genes and CancerPan-Cancer Atlas: project that has mapped 33 cancers and reclassifies tumor types based on molecular similarity, indicating the cell of origin – they group cancers by types of cells, not organThe genetic and environmental components in 15 common cancers were estimated using the nationwide Swedish Family-Cancer Database. Thyroid cancer: 53% Testicular: 25%Breast: 25%Cervical: 22%Melanoma (skin):21%Colon: 13% Lung: 8%

13. Hereditary Cancer SyndromesIf genetic testing was available and someone in your family had or has cancer, would you get tested to see if you also had an abnormality on this gene and what actions would you take if you tested positive?For example, celebrities Angelina Jolie and Christina Applegate had mastectomies (removal of the breasts) when they learned that they carried one of the genes for breast cancer (BRCA).However, only 10-30% of cancer cases are caused by heredityIn high-risk women, mastectomies can reduce the risk of breast cancer by 90%.

14. The Genetic Basis of CancerAs early as 1911, certain viruses were known to cause cancer.Oncogenes:Genes that cause cancer Found in virusesProto-oncogenes:Normal genes with the potential to become oncogenesFound in many animalsOften genes that code for growth factors, proteins that stimulate cell divisionFor a proto-oncogene to become an oncogene, a mutation must occur in the cell’s DNA.Most mutations arise in the organ where the cancer starts.In familial or inherited cancer A cancer-causing mutation occurs in a cell that gives rise to gametes The mutation is passed on from generation to generationBreast cancerBRCA1 or BRCA2 cancer genes – these are tumor suppressor genes that have mutated to become inactive. Keep in mind that often people who develop breast cancer might not have a family history of it.

15. Tumor-suppressor genesInhibit cell divisionPrevent uncontrolled cell growthMay be mutated and contribute to cancerTumor-suppressor genes function like repressors; think of cancerous cells as operons that are expressed: cancers appear when the repressors do not function.The development of a malignant tumor is accompanied by a gradual accumulation of mutations thatConvert proto-oncogenes to oncogenes Knock out tumor-suppressor genes

16. Note: For a proto-oncogene to become an oncogene, a mutation must occur in the cell’s DNA.

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18. 1mutationNormal cellMalignant cell4mutations3mutations2mutationsChromosomesAccumulation of mutations in the development of a cancer cell

19. Environmental Factors

20. Classifying Substances as CarcinogenicThe International Agency for Research on Cancer (IARC) is part of the World Health Organization. Its major goal is to identify causes of cancer. They evaluated the cancer-causing potential of more than 900 chemicals, placing them into one of the following groups:Group 1: Carcinogenic to humansGroup 2A: Probably carcinogenic to humansGroup 2B: Possibly carcinogenic to humansGroup 3: Unclassifiable as to carcinogenicity in humans (i.e., unknown)Group 4: Probably not carcinogenic to humansBased on how hard it can be to test these possible carcinogens, most are listed as being of probable, possible, or unknown risk. Only a little over 100 are classified as carcinogenic to humans.However… there are around 73,757 chemicals used commercially – industries are not required to test toxicity or carcinogenicity.

21. Mode of Action of CarcinogensMode of Action (MOA): how a chemical affects cells to promote the development of cancerGenotoxic: Carcinogens damage DNA/chromosomes directly; these can affect developing Cytoxic: Some carcinogens kill cells; the healing process can trigger cancer

22. Growth & Growth FactorsContact inhibition: normal cells stop dividing when touch each otherCancer cells lack this and grow on top of each otherMay be able to recruit normal cells to work with themOrdinary cells receive messages in the form of chemical growth factors to undergo cell division (mitosis).Cancer cells feed back growth messages to themselves.

23. Cancer DevelopmentInitiation Stage: Exposure to a carcinogen or an agent that damages a part of a cell’s DNA responsible for cell growth & division. Cancer may not develop as damage may be repaired, or the cell may be destroyed through apoptosis (programmed cell death), or by the immune systemPromotion Stage: The damaged cell will replicate, passing the damaged DNA to new “daughter” cellsProgression Stage: Cells replicate uncontrollably, form tumors by invading nearby tissues; may metastasize and spread to other organs or tissues.

24. Stages: InitiationSpontaneous or from exposure to a carcinogenCell is usually destroyed via apoptosis or immune systemImmune system can be suppressed by the carcinogen dioxinBrain cancer related to pesticides

25. Replication errorsBenzo[a]pyrene: a hydrocarbon that occurs when organic material is burned (such as coal, wood, tobacco, or meat). It sticks to the side of a strand of DNA, leading to replication errors during the next round of cell division. Every time a cell divides, it has to duplicate its DNA through a process called mitosis. Think of this as similar to transcribing (copying) a book over and over again – each time you rewrite it, you run the risk of making mistakes. Think of what would happen to the document if parts of the pages were stuck together.

26. Angiogenic genesAngiogenic genes control the creation of blood vessels.Although they are vital towards growth, development, and wound healing, they actually help tumors to transition from a dormant state to a malignant one. This lead to the use of angiogenesis inhibitors (some are a normal part of the body's control, some are administered as drugs).The tumors increase in size because angiogenic genes provide a constant supply of blood tothe tumor, meaning less water,oxygen and vitamins will be reaching the healthy tissues. Higher nutrient supplies means that cancer cells are less likely to die, thus maintaining the tumor’s size.

27. How the Immune System Prevents CancerSpecialized immune/ white blood cells can detect & destroy cancer cellsThese include natural killer cells, macrophages, and T cells.When cells of the immune system observe abnormal cells (such as bacteria, viruses, or the mutated cells that cause cancer), they send out chemical messages to bring more immune cells to the site. Some will place “tags” on the abnormal cell to mark it for destruction. Macrophages, or big eaters, will engulf the damaged cell through a process called phagocytosis, in which the cell is broken down by enzymes and destroyed.

28. PrimativismA cancer cell stops resembling the original differentiated cellThis is how the immune system can recognize and destroy the cell, but these cells are more virulent and have more genetic damageThese are more likely to spread Healthy melanocytes in tissue (compare the shapes, not the colors)Melanoma cells grown in a petri dish

29. Apoptosis: How the Cells Themselves Prevent CancerApoptosis: programmed cell deathIf the DNA of a cell is too damaged, enzymes will trigger a series of reactions leading to the death of the cell. This keeps damaged cells from proliferating and leading to cancer.However, this mechanism does not always work

30. Stages: PromotionTransformed cells escape detection from immune system Promotion: cancer cells waiting for exposure to cancer-stimulating substances – can take years after first contact with carcinogen/initiationCancer promoters encourage normal cells to divide by altering their genetic activity – mutations are not necessary; the cells are just encouraged to misbehaveEstrogen can act as a cancer promoter for cells with estrogen receptors – estrogen mimickers like BPA could do the same.Promoters can alter signal transduction – messages from outside the cell to the nucleus to trigger mitosis. This means more transformed cells made.

31. Stages: ProgressionMutations pile up and chromosomes become less stable – cells get new abilities instead:Capacity to spread and invade tissuesEnhanced sensitivity to hormonesAngiogenesisSubstances that can induce this include:ArsenicBenzeneAsbestosRadiation

32. Tissue RenegotiationStroma (Greek for “a mat to lie down on”): tissue that cells are onCancer can arise if tissues are poorly organized – no gene damage, just miscommunication Here’s a metaphor – a workplace should be made up of hard-working, honest people working together for the common good – just as cells in an organ such as the skin work together for a specific purpose – unfortunately, in one workplace, one of the workers goes crazy and starts giving out weird commands (“beat up the low-wage part-timers!”). Others listen to them, and start obeying these commands. Suddenly, the workers are all fighting and stop doing their jobs, leading to chaos. Some leave the job and start hassling others.… Cancer sucks.

33. What we’re seeing here is that the tumor cells, which would normally be controlled and killed off by the cells of the immune system, have now evaded and recruited the immune cells to help them form a tumor.

34. Cancer ClustersCancer cluster: a greater-than-expected number of cancer cases within a group of people in a geographic area over a period of time.Cape Cod: Elevated melanoma, prostate & breast cancer rates – may be related to pollutants from the Otis Air Force BaseSaugus, MA: multiple myeloma (a rare blood cancer) – may be from industrial pollutants from the RESCO waste management companyScituate, MA: leukemia, breast, kidney, testes, and liver cancer – may be because a municipal water well is located on an closed dump

35. Cancer-Causing Chemicals in Food Arsenic use in poultry production could increase cancer rates.  Arsenic is commonly added to poultry feed for the FDA-approved purposes of inducing faster weight gain on less feed, and creating the perceived appearance of a healthy color in the meat.  A 2013 study found that arsenic (a carcinogen) is present in raw and cooked chicken breast.  Researchers analyzing retail chicken breast samples found that concentrations were highest in conventional samples, and were significantly higher in cooked versus raw samples. The study tested chicken breasts sold under conventional, organic, and “antibiotic-free” labels.  Arsenic was detected in half of conventional chicken samples.  In “antibiotic-free” samples, 1 of 13 (8%) samples contained arsenic, and in certified organic samples, none were found. The study suggests that use of arsenic will result in 8,661 additional cases of cancer over 70 years, an average of 124 more cancers a year. 

36. Cancer-Causing Chemicals in Food Milk: Milk from recombinant-bovine growth hormone (rBGH)-treated cows has 10 times higher levels of IGF-1, a hormone that is a high risk factor for breast, prostate, colon, lung, and other cancers.Studies found that women under 50 with high levels of IGF-1 are 7 times more likely to develop breast cancer. Men with high levels of IGF-1 are 4 times more likely to develop prostate cancer.

37. Cooking Meat as Cancer RiskChemicals formed when muscle meat from beef, pork, fish, or poultry is cooked using high-temperature methods, such as pan frying or grilling directly over an open flame can increase cancer risks. In lab experiments, these have been found to be mutagenic—that is, they cause changes in DNA that may increase the risk of cancer. Cook meat well, but not too well – high temperatures (>300º) convert proteins into carcinogenic compounds:Heterocyclic amines (HCAs): formed when amino acids, sugars, and creatine react at high temperaturesPolycyclic aromatic hydrocarbons (PAHs): formed when fat and juices from meat grilled directly over an open fire drip onto the fire, causing flames. These flames contain PAHs that then adhere to the surface of the meat. PAHs can also be formed during other food preparation processes, such as smoking of meats.

38. But Everyone Loves Bacon!The IARC puts processed meat in Group 1 – Carcinogenic to HumansRed Meats are in Group 2A: Probably Carcinogenic to HumansPreservatives and chemicals added to processed meats can be carcinogenic.Note: Around 2 slices of bacon a day increases risk of colorectal cancer by 18% - so eat less.Limit red meat to two to three times a week.

39. Cancer-Causing Pesticides in FoodMirex and beta HCH are organochlorine pesticides which have been banned in the U.S. for decades, but are still found in measurable levels in some fish and dairy products. Endometriosis: painful condition where excess tissue that lines the womb grows outside of the uterus on other organs or structures in the body. It affects up to 10% of women. It also increases risk of diseases such as hypothyroidism, multiple sclerosis, chronic fatigue syndrome, and fibromyalgiaThere has also been an association with the disease to ovarian, breast, endocrine, kidney, thyroid, brain, and colon cancers as well as melanoma and lymphoma. Women with high levels of mirex in their tissues have a 50% greater risk of developing endometriosis, women with beta HCH have a 30-70% risk.

40. MirexMirex has been listed as a persistent, bio-acculumative, and toxic (PBT) pollutant by EPA; banned in 1978, it is a probable carcinogen that:Harmful to the stomach, intestines, liver, kidneys, eyes and thyroid gland Causes damage to the nervous system and the reproductive system May be the cause of increased miscarriages Used from 1962-1978 in the southeast US to control invasive fire ants. It is highly toxic to marine crustaceans, e.g., shrimps and crabs. It does not break down easily in the environment and becomes more concentrated as it moves up the food chain to humans and other animals. Mirex is not broken down in the body and is stored in our fat. Exposure through:Contaminated fish and shellfishBreast milkDrinking water

41. How Nutrition Can Reduce Your Risk of Cancer To quote Michael Pollan (“An Omnivore’s Dilemma”, and in Food Inc.): “Eat food, not too much, mostly plants.”Consume or cook with Vitamin A, Vitamin D, folic acid, and selenium, which repair DNA.Omega-3 fatty acids might help reduce tumor growthFiber helps remove waste products and toxins – such as carcinogens – from the body. The quicker these are out, the better.Cook with garlic, rosemary, sage and olive oil. These antioxidants block the formation of carcinogens that are produced when foods are cooked.

42. Nutrition cont.During photosynthesis, plants produce oxygen as a byproduct. This is good for us, but the oxygen molecule can split in half, producing the free radical, O. Phytochemicals: Plants produce compounds that may help prevent the build-up of free radicals in order to protect themselvesAntioxidants destroy the free radicals that might affect or damage DNA.

43. Developmental DisruptionChemicals can make developing cells more prone to cancer – these chemicals are not in typical lists of carcinogensDeveloping organisms have increased susceptibility to cancer if they are exposed to environmental toxicants during rapid growth and differentiation – such as in fetal development and childhood.Human studies have demonstrated clear increases in cancer after prenatal exposure to ionizing radiation, and there is evidence that brain tumors and leukemia are associated with parental exposures to chemicals. Animal experiments have demonstrated increased tumor formation induced by prenatal or neonatal exposure to a variety of chemicals, including direct-acting carcinogens and drugs.

44. ThalidomideA medication given to pregnant women that caused their babies to be born without arms: this is given early in pregnancy to prevent morning sickness – when the arms are developingIntroduced in Europe in 1957, doctors started noticing babies born with oddly-formed arms (phocomelia, or “seal limbs” – flippers). Banned in 1962 when the link was discovered. Never approved in the US.An enzyme in the medication kills off blood vessels leading to cell deathResearchers have been using thalidomide – under extremely controlled conditions – as treatments for cancer, leprosy, and HIV.

45. Thalidomide for Cancer Treatment? Anti-angiogenic: It prevents blood vessels from forming, therefore killing the cells that would be fed from the bloodstream. This prevents the tumors from forming.It also activates parts of the immune system (T-cells), which can help in the fight against the cancer cells.

46. HomeworkRead Ch. 18: Environmental Economics & Law; Ch. 9: Population & Urban Sprawl.Write a minimum of one page on the following scenario: Suppose scientists discovered that a chemical used in a specific, popular food causes cancer. Your friends and family ask you about this. Answer the following questions: What is cancer and how a chemical can cause it?Address public health concerns: How do you educate people and convince them not to eat a tasty food – will these efforts work? How should governments (federal, state, local) respond? Look at existing laws.Cite all sources –you are expected to explain cancer in scientific terms, and explain how environmental factors such as chemicals contribute to cancer development and need appropriate reference sources. This requires critical thinking as well as an understanding of environmental science.