Mutations, Environment, and Health

• UE2.5 - Public Health
• Course Fact Sheet No. 7
• Mutations and Environmental Changes

Environmental Modification: Impact Factors on Health

• Four factors have a potential health impact

Toxic Factors

• These include minerals like metals and carbon derivatives
• Carbon derivatives include fossil compounds from petroleum, coal, and gas and are generally from chemistry

Physical Factors

• Ionizing radiation causes significant impacts on health and environment
• Electromagnetic fields' undesirable effects are still being assessed

Psychosocial Factors

• Arise from tertiarization and deindustrialization in the West such as Europe and the USA
• New work organization/communication methods among employees
• Office work can cause conflicts that originate psychosocial illnesses like depression
• Other psychosocial illnesses include workaholism or intoxication from work
• Further examples are karoshi, burnout, moral harassment, chronic fatigue, and psychogenic syndromes

Biological Agents

• Stem from environmental modification
• They lead to reduced biodiversity and global warming
• Genetically Modified Organisms (GMOs) have positive effects on agriculture
• GMOs also have harmful effects on the environment
• An example is the Covid-19 crisis caused by Sars-cov2

Environmental Modification: Principal Mechanisms Involved

• Industry synthesizes around 100,000 molecules, renewing 10% annually

Concentration of Toxins

• Occurs through industries manufacturing accumulators
• Mercury is released, causing environmental intoxication that concentrates in fauna/flora and is consumed by the population

Dispersion of Pesticides

• Example: Atrazine remains in the environment for decades
• Impacts the health of people who consume contaminated water

Destruction of Environment

• Substances initially used as propellants in aerosol bombs destroy the ozone layer
• They are replaced by other molecules, which reforms the ozone layer

Endocrine Disruptors

• This encompasses dioxins, classes of molecules with representatives like PCBs and TCDD
• They are generated by combustion from carbon products like fossil compounds

Modification of Fauna and Flora

• Example: Creation of lagoons in Ephesus, favouring insect proliferation such as Anopheles which vector malaria
• This increase of malaria drastically reduced the population

Behavioral Phenomenon

• Industrialization and tertiarization originates psychosocial illnesses in telephone switchboards

Cancer and Carcinogenesis: Deleterious Effects - Epidemiology of Cancers in France

• Cancer cases nearly doubled between 1980-2010 which increased from 170,000 to 320,000 cases
• Given 800,000 annual births, 1 in 2 French people are at risk of developing cancer before death
• Reduced consumption of tobacco and alcohol has caused an observed reduction in cancer of the upper aerodigestive tract, esophagus, and stomach
• Hormono-dependent cancers are increasing such as breast, prostate and testicles

Origin of Two-Thirds Increase

• Improvements of genetic testing leads to better detection which explains around 20% increase in cancers like thyroid cancer
• A 25% increase of cancer diagnosis is attributable to population increase
• Aging population leads to increased cancer risks due to aging
• Environmental exposure to physical, biological, and toxic factors impacts cancer development

Possible Origin of Remaining Third

• Multi-parameter, with potential links to chemical pollutants similar to environmental estrogens such as plastics and pesticides
• These correlate with hormone-dependent cancers, are persistent, non-metabolized, highly volatile, circulate globally, and have a high affinity for fats
• Concentrating in fats, and may explain increased cancer rates due to accumulated quantities

Cancer Exposures

• Voluntary exposures include smoking and cosmetics with nanoparticles, where new reactive molecules could impact DNA in the first step of carcinogenesis
• Unavoidable exposures include food contaminated by dioxins released near incineration plants
• The dioxins can contaminate plants ingested by cows, ending up in milk

Mutagene and Carcinogene Evaluation

• The European REACH program studies 30,000 of the 100,000 produced molecules, representing large tonnages
• Toxicity is measured by the DL50 on rodents at doses that increase until half of the subjects die

Evaluation Problems

• Rodents' short lives (2 years) are not representative of humans long lifespans (80 years)
• Benzene, a long-term leukaemogen, and is not adjusted for toxic molecules at low doses
• The level of tolerable exposure in companies is reduced

Cancer and Carcinogenesis: Principles of Initiation

• Chemical instability is caused by molecules that pull electrons and transforms into a free radical

Consequences of Damage

• Formation of adducts on DNA, chromosomal breaks, and suppression of 5-methyl cytosine in non-coding regions
• Alkylations create bridges between DNA strands

Altered Replication

• Adducts and alkylations alter replication and promote mutations, plus expression of non-coding regions

Characteristics of Tobacco Smoke

• Tobacco smoke is a major, recognized carcinogen that is composed of 4500 carcinogenic molecules such as polycyclic aromatic hydrocarbons (PAHs), arsenic, and cadmium

Epidemiology

• 25-30% of the adult population smokes.
• Smoking incidence is presently increasing among women

Statistics on Death

• On average 1 in 2 smokers die of smoking related illness
• 200 die per day due to tobacco related illness
• It takes 20 years for a smoker to regain the life expectancy of a lifetime non-smoker

Smoking Related Illness

• The risk of lung cancer is 10x, totaling 20,000 cancers per year
• Increased risks of other digestive, hematological cancers, and cardiovascular diseases

Co-carcinogens

• Environmental exposure includes Radon gas which is radioactive and often trapped in basements.
• Radon gas is responsible for 10% of bronchopulmonary cancers.
• Professionals such as those in asbestos and chrome, increase risks of cancer in smokers and passive smokers

Passive Smoking

• Passive smoking represents a 20% increase

Characteristics of Newly Confirmed/Suspected Carcinogens

• Relative risk = 1-1.5 for dioxins
• 10-15% risk in cases of professional or environmental exposure

Several Target Organs

• Unlike older carcinogens are less targeted and cause several types of cancers
• Asbestos causes lung cancers

Elevated Latency

• Act for a long period at low doses over a decade before the cancer diagnosis
• Example: Electromagnetic fields

Novelties

• Few are known about these new molecules, like nanomaterials, structures ordered in nm
• These are highly reactive due to their sizes and require further studies

Notion of Acceptable Risk

• This is linked to the risk of exposure where a given carcinogen can't be supressed
• Acceptable that 1 person dies following exposure to carcinogen in 100,000 people (10^-5) in Southern Europe
• The above risk is 1 in 1,000,000 (10^-6) in Northern Europe

Example of Benzene

• Benzene replaces lead in gas and is rapidly degraded in the environment
• The acceptable leukaemogenic risk is 1/100,000

Reprotoxicity and Environment: Hypofertility - Sterility

• Conception impossible for 10% and difficult for 15% of couples

Clinical Trends

• Incidence may have increased in recent decades
• Spermatozoa counts are on decline, with 100 million/ml at the end of WWII decreased by 30-50%

Etiological Factors Include

• Physical factors like shift work, ionizing radiation, and heat
• Psychological factors like dystress
• Chemical pesticides and solvents

Congenital Malformations and Anomalies

• Distilbene: A hormone prescribed in the 1950s to improve pregnancies
• Adverse effects were shown up to the third generation; rare genital cancers in children and anomalies in young children

Clinical Observations

• Examples include: cryptorchidism (undescended testicles) and Hypospadias (abnormal urinary tube placement)

Toxic Exposure

• Toxic exposures, like those that are estrogen-like, modify secretions in males needing androgens
• This causes negative effects at trace levels, concentrates in the mother's fats before conception, and probably due to part per million (PPM) or billion (PPB)

Emerging Infectious Diseases

• Recombined viral strains are exemplified by the influenza pandemic immediately following World War I and COVID-19
• Whooping cough and measles are diseases made more likely because of a lack of vaccinations

Nosocomial Infections

• These are correlated with antibacterial resistance, and decreased immune system efficacy
• This is due to dioxins that require development of new antibacterial treatments

Diseases of the Past May Reappear

• The diseases and pathogens can reappear in impoverished settings, degradated facilities
• Additionally diseases can reaprear when treatment systems are altered
• Example diseases: plague, cholera, typhoid, and typhus

Climate Change will Redistribute Diseases

• Dengue and Chikungunya which causes an epidemic of West Nile in 2005 in New York which caused dozen of deaths

Biotechnology and its Consequences

• Vaccine development using civilian derived virus strains
• Possible developments for covert warfare, like using silent or time delayed virus strains

Civilizations Disappear Because of Diseases

• Peste was the most likely reason behind the the Greek culture's demise during the IV century
• A third of the world's population died because of an ebola mutation that spread during the middle ages causing the Mongols downfall