Environmental Toxicology and Cancer

Environmental Toxicology and Cancer Overview

• Environmental toxicology and cancer involves studying environmental toxicants, pharmaceuticals, and the process of chemical carcinogenesis.

Environmental Toxicants

• Environmental toxicants are chemicals released into the environment that can harm living organisms.

Acute vs. Chronic Toxicity

• Acute toxicity is from a single exposure to a chemical, often at a high dose, with an example being a chemical spill.
• Chronic toxicity arises from repeated exposure to small doses of a chemical over time, such as eating contaminated food.

Aflatoxin B1 Example

• Acute effects of Aflatoxin B1 include liver necrosis, liver failure, and death.
• Chronic exposure to Aflatoxin B1 can lead to liver cancer

Air Pollution

• Air pollution's history is long and complex, divided into particulate matter and gaseous air pollutants.
• Both natural and anthropogenic sources contribute to air pollution.
  • Natural sources include volcanoes, forest fires, prairie fires and dust storms.
  • Anthropogenic sources include heating and power, automobiles, and industrial processes
• 1273: Edward I of England made burning coal illegal when parliament was in session, punishable by decapitation.
• Early 1900s: Automobiles increased rapidly, making gasoline internal combustion engines a major pollution source.
• 1952: "Killer smog" in London caused 4,000 deaths from respiratory illnesses, leading to the Clean Air Act.
• 1956: The Clean Air Act introduced measures such as shifting to cleaner fuels for home heating.

Major Air Pollutants

• Particulate matter includes tiny nongaseous particles that can be solid or liquid.
• Gaseous air pollutants include carbon monoxide, carbon dioxide, nitrogen oxides, sulfur oxides, hydrogen sulfide, and ozone.
• Heating and power plants using fossil fuels release carbon dioxide, carbon monoxide, sulfur oxide, and nitrogen oxides, with coal as the largest contributor to human-made carbon dioxide increase.
• Automobile exhaust emits smoke, lead particles, carbon monoxide, and nitrogen oxide.
  • Regulations in the late 20th century aimed to reduce these emissions with low-lead gasoline, emission testing, and green vehicles.
• Industrial processes release various pollutants like acids, solvents, and metals, depending on the manufacturing.

Health Impact of Air Pollutants

• Air pollution primarily causes chemical irritation of the respiratory tract.
• Young children, older adults, and those with cardiorespiratory issues like asthma are more susceptible.
• Health problems generally are a result of combined particulates and sulfur oxides.

Tobacco Smoke

• Environmental tobacco smoke (second-hand smoke) combines mainstream and sidestream smoke.
• 2002: The International Agency for Research on Cancer concluded second-hand smoke causes lung cancer after reviewing accumulated evidence.
• Exposure to environmental tobacco smoke carries similar health risks to direct smoking.
• Bylaws restrict smoking in public to protect non-smokers.

Pesticides

• Pesticides are intentionally used to kill organisms.
• Insecticides and herbicides are major classes of pesticides that act as environmental toxicants.

Insecticides

• Insecticides are chemicals that kill insects or impair their reproduction/development.
• There are many types of insecticides.

Organochlorine Insecticides

• These insecticides increase CNS stimulation, causing tremors, convulsions, and death by affecting neuron sensitivity.
• Organochlorine insecticides pose long-term environmental problems, and have largely been phased out.
• DDT (dichlorodiphenyltrichloroethane) was introduced in 1945 to control malaria mosquitoes.
  • It was widely used until the 1970s when its use stopped due to resistance from insects, decline in bird and fish populations, increased DDT concentrations, and heightened DDT levels in food.

Organophosphorus Insecticides

• Originally created as warfare agents during WWII.
• Selective types like Malathion require metabolic activation and break down quickly, thus posing less environmental risk.
• Organophosphorus insecticides are very toxic to humans, absorbed through the skin, and a leading cause of poisoning in agriculture.
• They irreversibly inhibit acetylcholinesterase, which breaks down acetylcholine in the synaptic cleft.
• Inhibition results in increased acetylcholine, leading to decreased heart rate, breathing issues, incontinence, blurred vision, and potentially respiratory failure.

Herbicides

• Herbicides are pesticides designed to kill or harm plants.

Agent Orange

• Agent Orange was used heavily in the Vietnam War as a defoliant to expose targets.
• It mimics plant growth to cause plant death.
• It contains TCDD (2,3,7,8-tetrecholorodibenzodixon), which is introduced during manufacturing.
• TCDD binds to the aryl hydrocarbon receptor, altering normal cellular functioning.
• TCDD toxicity causes chloracne, liver damage, CNS impairment, increased cancer risk, and birth defects/stillbirths.
• 2004: Ukrainian president was believed to be poisoned with TCDD, with blood levels 50,000 times higher than average.

Paraquat

• Paraquat is a widely used but highly toxic herbicide if ingested.
• Causes cellular damage and immediate burns to the mouth and stomach.
• Paraquat's primary target is the lungs, leading to fibrous tissue development and breathing difficulty. Ingesting only two teaspoons can cause death due to lung damage.

Toxic Effects of Specific Chemicals

• Specific chemicals in the environment can harm humans; lead, mercury and bisphenol A (BPA) are three common examples.

Lead

• Lead is a naturally occurring element found in lead oxide and tetraethyl lead compounds.
• Exposure sources include old paint, where it was used to quicken drying, improve wear, and enhance color vibrancy in the 1950s.
• Children absorb 35-50% of ingested lead, while adults absorb only 10%, making children more susceptible to lead toxicity.
• Lead-acid car batteries account for the largest proportion of global lead consumption, Air emissions from industries end up in soil.
• Lead contaminates fruits, vegetables, and soil, creating pathways for exposure.
• Lead impacts multiple systems in the body
  • CNS effects include decreased appetite, irritability, and fatigue, that can eventually cause permanent brain damage (lead encephalopathy), learning deficits, epilepsy, and blindness.
  • PNS degeneration results in loss of coordination and clumsiness.
  • Kidney dysfunction is due to impaired energy metabolism that is reversible if lead exposure stops.
  • Blood decreases heme biosynthesis, reducing red blood cell lifespan and causing anemia; this is a reversible effect.

Mercury

• Mercury is a naturally occurring element found in water and air.
• The main source of mercury contamination is industry with use for preparation of chlorine and sodium hydroxide as an electrode.
• Exposure happens through air (mercury vapor) or food.
• The major sources of exposure for humans is eating fish from mercury contaminated water.
• Mercury has two toxic forms: mercuric mercury and methyl mercury
  • Exposure to mercuric mercury is through vapor inhalation.
    • Only 15% is absorbed, but it accumulates and damages kidneys.
  • Mercury is converted to methyl mercury by bacteria in fish water, with 90% absorption from food
    • It targets and damages the CNS, leading to irritability, numbness, altered senses, tremor, paralysis, coma, and death
• Chelating agents are used for mercuric mercury poisoning, but not for methyl mercury poisoning.
  • Charcoal can prevent absorption of methyl mercury if ingested recently, but is ineffective once is irreversibly absorbed

Minamata Disease

• Minamata disease occurs from mercury poisoning, named after the sickness of those living in Minamata Bay, Japan.
• The chemical came from wastewater dumped by the Chisso Corporation as methyl mercury poisoning, contracted primarily through consumption of fish in the bay.
• Symptoms included numbness of limbs and neurological effects
• Minamata disease is considered the first sickness caused by environmental pollution in Japan.
• About 2,300 people were recognized as victims in Kumamoto and Kagoshima Prefecture with around 1900 deaths, and 2000 still awaiting recognition.

Bisphenol A

• BPA is an industrial chemical for hard, clear plastics, particularly polycarbonates, in reusable water bottles and baby bottles
• It appears in epoxy resins as a protective lining for metal food and beverage cans.
• Exposure is through diet where minute quantities could leach out, exacerbated by microwaving.
• BPA has estrogen-like activity by binding to estrogen receptors to mimic estrogen
• BPA has been proposed to play a role in reproductive cancers, infertility, and altered brain development in infants.
• Health Canada has determined that current dietary exposure poses no health risk to the general population, even newborns and infants
• Infants are at the greatest risk of exposure due to their small size.
  • Canada is working to increase protection of infants and young children by prohibiting BPA in baby bottles and decreasing levels in infant formula cans.
• Environmental concerns exist due to BPA accumulation in water harming fish and other organisms.
  • Environment Canada has proposed regulations to limit BPA concentrations and handling/disposal protocols.

Pharmaceuticals in the Environment

• Increased usage over the last five decades has led to pharmaceuticals being recognized as relevant environmental pollutants; concentrations are generally low in surface water.
• Potential adverse effects on human health are known due to clinical studies but affect aquatic animal and plantlife more.

Antibiotics Use in Agriculture

• The use of antibiotics in agriculture responsible for rising levels in ground water and soils, with contamination occurring via excretion and manure spreading.

Pharmaceuticals and Pets

• Treatment in companion animals can impact surface and groundwater.

Disposal of medication

• About 25% of all unused medicines get washed down the sink or flushed down the toilet, while another 30% end up in landfills.

Pharmaceutical Antibiotics in Aquaculture

• Used to prevent disease and promote rapid growth
• Aquaculture’s concentrated operations raise local antibiotic concentrations

Human Prescriptions

• One of the major sources of pharmaceuticals in the environment
• Administered drugs are excreted unchanged or as active metabolites
• Drugs are passed into wastewater systems that are not fully capable of removing them

Manufacturing

• The discharge from manufacturing plants has a major effect in local surface and groundwater.
• This will increase over time as facilities move to developing countries with less environmental standards.

Major Classes of Pharmaceuticals in the Environment

• Neuroactive drugs: increased by 60% over the last decade, and found in surface water, groundwater, and soil.
  • Sewage treatment is not fully capable of removing neuroactive drugs.
  • At high levels, SSRIs have deleterious effects on the reproduction and physiological development of fish.
• Steroid hormones: estrogenic compounds from oral contraceptives and excretion by animals.
  • Concentrations are low, but there is concern over the additive effect of human exposure to estrogen and endocrine disrupting agents.
  • Low concentrations of hormones may affect reproductive capacity and sexual maturation of aquatic animals, such as ethinyl estradiol.
• Antibiotics: major source is use in agriculture which enhances animal growth
  • This can lead to the development of resistant strains of bacteria.
• Antihypertensive drugs: 30% of Canadians are treated daily for hypertension.
  • Concentrations are low, but questions remain about biomagnification in the food chain.
• Analgesics: ibuprofen, naproxen and ASA are the most commonly observed in the environment
  • At the present concentration, there is no threat to human health and exhibit minimal effects on aquatic environments.

Environmental standards

• There are standards for permissible levels of pesticides in drinking water but no pharmaceutical regulations
• Human exposure occurs through drinking water and bioaccumulation in food sources.
• Factors impacting the concentrations of a given pharmaceutical
  • The volume of use
  • Dosage administered
  • Persistence in the surrounding environment
  • Ability of the agent to be removed in sewage treatment
• The minimum therapeutic dose is used for determining the risk
• Anticancer drugs are the exception to The minimum therapeutic dose as risk assessment.
• Overall, research suggest exposure to the human population to pharmaceuticals appears to pose no a health risk.

Cancer and Chemotherapeutics

• Primarily affects Canadians 50 years of age or older.
• 45% of males and 43% of females will develop cancer and one in 2.3 people.
• 30% of deaths in Canada are due to cancer, with lung cancer being the leading cause.
• Cancer is a generic term for a large number of diseases that involve abnormal group of cells are share key features

Key Features of Cancer Cells

• Cancer defined as an abnormal cells sharing the key features
  • Cell growth & division: the ability to proliferate indefinitely
  • Invasion: the ability to invade surrounding normal tissue
  • Metastasis: the ability to spread throughout the body Causes of Cancer
• Cancer arises due to two interacting causes: genes and environmental factors

Genes

• Genes: Genetic make up influences a variation in response to carcinogens
  • Having a gentically-based deficiency in DNA makes one prone to mutation

Environmental

• Environmental Factors: Non-genetic elements such as environmental chemicals, diet, and infections -These Factors: Modifiable, meaning a person can decrease the risk of exposure to detrimental environmental factors

Steps in Carcinogenesis

• Carcinogenesis=Development of cancer
  • Multistage process with three main steps

Initiation

• Initiation-Starts with procarcinogen, and ends with either a normal cell or a cancer cell
  • Procarcinogens- Environmental carcinogens, inactive chemicals Procarcinogens- Undergo metabolic activation by drug metabolizing enzymes in the body Ultimate Carcinogens- Highly reactive forms of chemicals If the DNA damage properly repaired returns to normal cell If not permanent DNA damage occurs and change in the chemistry of the gene area

Promotion

• Promotion- Compounds that promote division and proliferation of the cell Promotors-Minimal effect on uninitiated cells

Progression

• Rapid growth of tumors once they are established, increasing the malignancy of the tumor
• A long latent period occurs between exposure and development of disease

Environmental Factors and Cancer Risk

• Tobacco use causes cancers including lung, esophageal, bladder, and pancreatic cancers.
  • Depending on the cigarettes smoked, frequency , and the habit lead to cancer results
  • Smokers: eight times more likely to develop lung cancer than non-smokers. -Passive Smoking: a risk factor for cancer; more than 800 Canadians who do not smoke die from second hand smoke every year.High
• Adult Diet :Saturated animal fat/Red meat strongly linked to colon, rectum, and prostate cancers
  • intake of salt have been linked to other cancers
• Occupational Factors strict control measures have cut down on the exposure - Developing nations have less measure in place

Viruses and infection

• Two main Virus types cause cancer
  • Helicobacter pylori- Stomach ulcers, strongly associated with stomach cancer. -Hepatitis. B/Hepatitis C- Liver cancer/Globally, 80% of liver cancer. HPV- Cervical cancer

Cancer Prevention: Modifiable Risk Factors

• Avoid excessive Sunlight
• Monitor alcohol Intake
• Eliminate Tobacco Use
• Eat Healthy
• Be Active
• Get Vaccinated

Goals of Cancer Treatment

• Prevent Cancer- Stop cell growth, or remove precancerous cell.
• Cure the cancer-primary Cure Achieved- few areas achieved

Control the Cancer:

• Goal, stopping it from growing and spreading, and prolonging patient survival.
• Relieve The Symptoms: Important to make the patient as comfortable as possible. Includes:Medications for symptoms like pain or nausea.

Drugs Used For The Treatment of Cancer

• Main types of cancer: Surgery, Radiation and bone marrow transplantation Chemotherapeutic Drugs: Act by slowing rapidly dividing cells -Inhibit DNA synthesis, protein synthesis, or cell division through a variety of ways Newer agents-Directly against abnormal protein in cancer cells.
• Several Classes of Chemotherapeutic drugs exist, ranging in the specificity of their targets

Chemo Drug Types

• Alkylating agents-Bind to and interfere with DNA replication
• Mitotic inhibitors-Affect microtubule function and the formation of the mitotic spindle, thereby preventing cell division
• Hormones And Hormone Antagonists-Hormone sensitive tumors/Suppressing cell division Biologicals-Derived through molecular biological techniques
• Cancer Cells: divide continuously

Principles of Cancer Chemotherapy

• Benefit-Risk Assessment: -What’s the benefit versus adverse effects of the chemotherapy treatment
• Combination Chemotherapy: Used combination for a couple of reason

Side effects.

• Development Of Resistance: Cancer cells development of resistance
• Occurrence Of toxicities Chemotherapeutic Drugs: If a single combination allows for different toxicities