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ENVIRONMENTAL DISEASE - Moore

LIVING WITH THE EARTH

ENVIRONMENTAL DISEASE - Moore

Objectives for this Chapter

A student reading this chapter will be able to:
1. Discuss and define the concepts of environment and disease.
2. List and explain the factors influencing environmental disease including infectious disease, physical and chemical injury, ionizing radiation, developmental disease, neoplastic disease, and nutritional disease.

ENVIRONMENTAL DISEASE - Moore

Objectives for this Chapter

3. Explain the process of genetic replication in mammalian cells. List the major genetic components and discuss their primary actions and features.
4. Describe and discuss the major mechanisms of developmental and genetic diseases.

ENVIRONMENTAL DISEASE - Moore

Objectives for this Chapter

5.Describe and provide a schematic of the new processes in recombinant-DNA and genetic screening techniques.
6. Discuss and describe the new concepts on the origins of cancer, risk factors, and current trends.

ENVIRONMENTAL DISEASE - Moore

LIVING WITH THE EARTH

ENVIRONMENTAL DISEASE

Introduction

We continue to manufacture and disperse billions of tons of over 70,000 potentially toxic chemicals into the biosphere without regard for nature or an appreciation of the danger that these chemicals can bring to our earth or to us.

ENVIRONMENTAL DISEASE - Moore

LIVING WITH THE EARTH

ENVIRONMENTAL DISEASE

Introduction

Love Canal: Declared an emergency in 1978
Times Beach Missouri: Dioxin contamination discovered in 1982

ENVIRONMENTAL DISEASE - Moore

LIVING WITH THE EARTH

ENVIRONMENTAL DISEASE

Introduction

Carcinogen
Any chemical known to cause cancer.
Nearly 90 percent of cancers can be traced to an environmental cause and so may be largely preventable.

ENVIRONMENTAL DISEASE - Moore

What are the messages given through the public media about toxic chemicals?

Exposure to toxic chemicals have dramatically increased the risk of cancer.
Common household and agricultural chemicals are causing many human diseases and death.

ENVIRONMENTAL DISEASE - Moore

What are the messages given through the public media about toxic chemicals?

Polluted air and water are major sources of disease risk.
Environmental chemicals are interfering with the reproductive process in humans and producing harmful effects in the fetus and young children.

ENVIRONMENTAL DISEASE - Moore

Defining the Term Environment in Relation to Disease (Cancer)

Environment
Personal and cultural behavior including smoking, diet, alcohol consumption, sexual and reproductive patterns, workplace, infections, food additives, and pollution along with the strictly physical environment.

ENVIRONMENTAL DISEASE - Moore

Some of the Major Factors associated with Cancer
(Fig. 4.1)

Diet
Tobacco
Infection
Sexual behavior
Occupation

ENVIRONMENTAL DISEASE - Moore

Fig. 4.1

Adapted from Morbidity and Mortality Weekly Report. 15

ENVIRONMENTAL DISEASE - Moore

Pollution

Pollution may be defined as the presence of a foreign substance - organic, inorganic, radiological or biological - that tends to degrade the quality of the environment so as to create a health hazard.

ENVIRONMENTAL DISEASE - Moore

Defining Disease

A definite pathological process having a characteristic set of signs and symptoms which are detrimental to the well-being of the individual.

ENVIRONMENTAL DISEASE - Moore

Disease Terminology

Endemic
Diseases that already exist in a community where it is maintained in a low but constant incidence.
Epidemic
Marked increase in incidence of disease within limited area affecting ever-increasing number of people

ENVIRONMENTAL DISEASE - Moore

Disease Terminology

Pandemic
An epidemic spread throughout the world, as in the case of various outbreaks of influenza.

ENVIRONMENTAL DISEASE - Moore

Disease Terminology

Acute Disease
Having a rapid onset, is usually self-limiting, and are of relatively short duration.
Chronic Disease
Having a slow onset and lasting for extended period of time. (i.e. cancer, emphysema, some forms of heart disease, or AIDs)

ENVIRONMENTAL DISEASE - Moore

Defining Disease

Infectious Disease
Infectious diseases result from the pathologic process occurring when a microbial agent invades the body.

ENVIRONMENTAL DISEASE - Moore

Infectious Disease

Reservoirs
Sources of disease which can be living organisms or inanimate objects that provide the conditions where the organisms may survive, multiply, and also provide the conditions necessary for transmission.

ENVIRONMENTAL DISEASE - Moore

Infectious Disease

Carriers
People who may or may not exhibit symptoms, but harbor and transmit the disease organisms.
Zoonoses
Diseases that are spread from animals to humans, such as Lyme Disease.

ENVIRONMENTAL DISEASE - Moore

Infectious Disease

Major Routes of Infection
Contact
Vehicles
Vectors

ENVIRONMENTAL DISEASE - Moore

Major Routes of infection

Contact
Direct Contact Transmission (person-to-person)
Indirect Contact Transmission (cups, needles)
Droplet Infections (sneezing, coughing-droplets travel less than one meter)

ENVIRONMENTAL DISEASE - Moore

Major Routes of infection

Vehicle
Disease agents that are transmitted by various media such as air, water, food, intravenous fluids or blood, and drugs.

ENVIRONMENTAL DISEASE - Moore

Major Routes of infection

Vectors
Animals that carry pathogens from one host to another, either from another human that is infected or from an infected animal.

ENVIRONMENTAL DISEASE - Moore

Major Routes of infection

Vectors
Mechanical Transmission (foot pads)
Biological Transmission (biting insects and agent reproduces in vector)
Types of Hosts
Definitive Host (sexual cycle of disease agent takes place in definitive host - mosquito for malaria)
Intermediate Host (asexual cycle - humans for malaria)

ENVIRONMENTAL DISEASE - Moore

Physical and Chemical Injury

Physical Injuries include:
Mechanical Injury
Thermal Injury
Ionizing Radiation

ENVIRONMENTAL DISEASE - Moore

Physical and Chemical Injury

Major mechanisms for chemical Injury are:
Interference with enzyme activity
Directly combining with some cell component other than enzymes
Producing a secondary action in which a chemical causes the release or formation of a more harmful substance

ENVIRONMENTAL DISEASE - Moore

Developmental Disease

Every individual within each species is very much a representation of the information contained in the genome together with the expression of those genes in the development of that individual.

ENVIRONMENTAL DISEASE - Moore

Developmental Disease

Developmental disease occurs when faults or mistakes occur within the genes (or chromosomes), or stages in development of the fetus are disturbed.

ENVIRONMENTAL DISEASE - Moore

Developmental Disease

Major Categories of genetic disease include:
Single gene defects
Cytogenic defects

ENVIRONMENTAL DISEASE - Moore

Developmental Disease

Cytogenic Defects are:
Abnormalities in the number or structure of chromosomes
Teratologic Defects are:
Defects which arise during the embryonic period of development. Causative factors are usually not genetic but from exposure to chemicals or radiation (teratogens)

ENVIRONMENTAL DISEASE - Moore

Neoplastic Disease

Neoplasia
The new and uncontrolled growth of abnormal tissue from the transformation of normal body cells.
Tumors
The growth of cells as a result of neoplasia, also called a neoplasm.
Tumors may be malignant or benign.

ENVIRONMENTAL DISEASE - Moore

Malignant Tumors

Exogenous Factors-arising from the environment
Habits (tobacco use, poor nutrition, alcohol use, sexual and reproductive activities)
Ionizing radiation
Chemical exposure
Environment (socio-economic, geographical, and occupational)
Oncogenic viruses

ENVIRONMENTAL DISEASE - Moore

Malignant Tumors

Endogenous Factors-originating from within the body
Gender
Age
Hormonal imbalance
Impaired immune system
Genetic predisposition

ENVIRONMENTAL DISEASE - Moore

Nutritional Disease

Malnutrition, as a consequence of inadequate diet, is often associated with ignorance and poverty which are manifestations of a weakened society.

ENVIRONMENTAL DISEASE - Moore

Nutritional Disease

Kwashiorkor
Caused by a lack of protein in children 1-3 years old.
Marasmus
Caused by lack of food in children one year of age.
Scurvy
Caused by the lack of vitamin C.

ENVIRONMENTAL DISEASE - Moore

Environmental Disease

Any pathologic process having a characteristic set of signs and symptoms which are detrimental to the well-being of the individual and are the consequence of external factors, including exposure to physical or chemical agents, poor nutrition, and social or cultural behaviors.

ENVIRONMENTAL DISEASE - Moore

THE ROLE OF GENETICS IN DISEASE

Structure and Function
This thread of life is deoxyribonucleic acid (DNA), a spiral, staircase-shaped molecule over 3 billion steps long compressed in the nucleus of living cells.
The storage and transcription of biological information occurs within DNA which has the power to express that biological information in the form of proteins.

ENVIRONMENTAL DISEASE - Moore

Structure and Function

DNA is located within the cell nucleus of each of the human body’s 100 trillion cells (except mature red blood cells) (Fig. 4-2).
Each nucleus contains 46 chromosomes arranged in 23 homologous pairs.

ENVIRONMENTAL DISEASE - Moore

Fig. 4-2

Adapted from Elmer-Dewitt. 20

ENVIRONMENTAL DISEASE - Moore

Structure and Function of DNA

DNA is a very long, thread-like molecule which is formed by four recurring subunits called mononucleotides.
Nucleotides are identical and attached to each other in a long chain by phosphodiester links between carbon atoms in each molecule (Fig. 4-3).

ENVIRONMENTAL DISEASE - Moore

Fig. 4.3

ENVIRONMENTAL DISEASE - Moore

Structure and Function of DNA

Four different recurring mononucleotides are the base elements of the DNA coding system (Fig. 4-4).
Adenine and Guanine (purines)
Thymine and cytosine (pyrimidines)

ENVIRONMENTAL DISEASE - Moore

Structure and Function of DNA

Pair nucleotide bases fit together in a precise way, held together by hydrogen bonds between the base pairs and by hydrophobic bonding (Fig. 4-4).

ENVIRONMENTAL DISEASE - Moore

Fig. 4.4

ENVIRONMENTAL DISEASE - Moore

Replication

Dividing cells provide each daughter cell with one complementary strand of the parent DNA and then synthesize a complementary strand to produce double-stranded DNA.

ENVIRONMENTAL DISEASE - Moore

Structure and Function of DNA

Proteins
Proteins are composed of specific sequences of amino acids linked by peptide bonds
Enzymes are proteins
Proteins that interact with a substrate much like a key in a lock to catalyze the formation of a new molecule or product.

ENVIRONMENTAL DISEASE - Moore

Protein Biosynthesis

DNA must first be transcribed to another molecule called messenger RNA or mRNA before it can reach the ribosomes outside of the cell.

ENVIRONMENTAL DISEASE - Moore

Protein Biosynthesis

Codons
A group of 3 nucleotide bases which specifies the position of one amino acid in a protein molecule.
Anticodons
The recognition site for specific codon triplet (Fig. 4-5).

ENVIRONMENTAL DISEASE - Moore

Fig. 4-5

Adapted from Lehninger. 21

ENVIRONMENTAL DISEASE - Moore

Diseases of Genetics and Development

Genetic Abnormalities
Mutation
A change in the nucleotide base sequence of DNA.

ENVIRONMENTAL DISEASE - Moore

Genetic Abnormalities

Many human diseases are associated with genetic defects (Fig. 4-6).
Single-gene defects known as point mutations or base substitutions.
Cytogenetic defects are abnormalities in the number or structure of chromosomes.

ENVIRONMENTAL DISEASE - Moore

Fig. 4-6
point mutations

Adapted from Elmer-Dewitt. 20

ENVIRONMENTAL DISEASE - Moore

Genetic Abnormalities

Spontaneous Mutation
Point mutations that occur spontaneously because of occasional mistakes created in the process of DNA replication without any intervention of external factors.
Mutagens
Agents in the environment including chemicals or radiation that promote mutations.

ENVIRONMENTAL DISEASE - Moore

Genetic Abnormalities

Dominant Genes
The genes are always expressed phenotypically (physical appearance). (Huntington’s disease)
Co-dominant Genes
Partly expressed if present as a single allele. (Sickle cell disease)

ENVIRONMENTAL DISEASE - Moore

Genetic Abnormalities

Recessive Genes
A defective gene must occur in both chromosomes at complementary sites in order for the disease to be expressed. (PKU, cystic fibrosis)
Cytogenetic Defects
Abnormalities in the number or structure of the chromosomes. (Trisomy 21)

ENVIRONMENTAL DISEASE - Moore

New Approaches in Genetics

Methods of Studying Genes
Genetic Engineering is science of creating recombinant DNA, which permits the transfer of genes between unrelated species.

ENVIRONMENTAL DISEASE - Moore

Methods of Studying Genes

Restriction enzymes are enzymes used to cut DNA into several predictable and reportable pieces (Fig. 4-7).
Insulin is genetically engineered using restriction enzymes and cloning vectors (plasmids) (Fig. 4-8).

ENVIRONMENTAL DISEASE - Moore

Fig. 4-7

Adapted from Tortora et al.. 25

ENVIRONMENTAL DISEASE - Moore

Fig. 4-8

Adapted from Tortora et al.. 25

ENVIRONMENTAL DISEASE - Moore

Methods of Studying Genes

In addition to making products, recombinant-DNA technology can produce millions of exact copies (cloning) useful in analytic techniques such as hybridization (Fig. 4-9), or genetic screening (Fig. 4-10).

ENVIRONMENTAL DISEASE - Moore

Fig. 4-9

Adapted from Tortora et al.. 25

ENVIRONMENTAL DISEASE - Moore

Fig. 4-10

Genechip technology has greatly simplified this task. This single-use probe array has 1000ds of different oligonucleotide probes.

Affymetrix, Inc.

ENVIRONMENTAL DISEASE - Moore

The Hunt for Environmental Genes

Saran nerve gas attack by Shinryko cult members in Tokyo subway (1995) revealed variations in genes coding for paraoxonase enzyme. Ten % of Caucasians and 25% of Asians produce enzyme that is 10X better at detoxifying paraoxonase.
Variations in genes coding for P450 and NAT genes can increase cancer bladder risk 6X in smokers.

ENVIRONMENTAL DISEASE - Moore

The Promise of Genetic Therapy

Gene therapy may involve removing cells with defective genes from a person and replacing those genes with normal or healthy genes and then placing the cells back into the patient.

ENVIRONMENTAL DISEASE - Moore

The Ethical Dilemma

The discovery of defective genes is progressing at a much faster pace then the development of other treatments and gives rise to many ethical and legal dilemmas.

ENVIRONMENTAL DISEASE - Moore

CANCER – WHAT IS IT?

Most cancers develop from the interaction of genetics with environment and perhaps less than five percent can be attributed to hereditary factors alone (Fig. 4-11).

ENVIRONMENTAL DISEASE - Moore

CANCER – WHAT IS IT?

Cancer produces its damaging effects through:
local damaging effects;
metastasis; and
systemic effects.

ENVIRONMENTAL DISEASE - Moore

CANCER – WHAT IS IT?

Metastasis
A process where malignancies travel producing tumors at distant sites.

ENVIRONMENTAL DISEASE - Moore

How Does Cancer Develop?

In a typical pathway leading to cancer, a chemical agent combines with human DNA to form an adduct (carcinogenic residues bound to DNA) which leads to increased mutations that may eventually accumulate and lead to cancer.

ENVIRONMENTAL DISEASE - Moore

Fig. 4-11

Adapted from Perera. 10

ENVIRONMENTAL DISEASE - Moore

How Does Cancer Develop?

Oncogenes
Defective genes that produce proteins that inappropriately stimulate cell division.

ENVIRONMENTAL DISEASE - Moore

How Does Cancer Develop?

Spell-checker proteins
When DNA is replicated, spell-checker proteins correct errors in the DNA. If the Genes that code for these proteins are defective, the spell-checker does not function correctly (Fig. 4-12).

ENVIRONMENTAL DISEASE - Moore

Fig. 4-12

ENVIRONMENTAL DISEASE - Moore

How Does Cancer Develop?

Apoptosis
The process of cellular self-destruction when cell damage accumulates to the point where cell integrity is compromised.
One of the most important genes coding for enzymes involved in apoptosis is p53, a tumor suppression gene.

ENVIRONMENTAL DISEASE - Moore

How Does Cancer Develop?

Mutations occurring along the p53 gene appear at characteristic sites with unique base sequences known as biomarkers.
The p53 gene halts cell division until DNA can be repaired, or turns on the mechanism for cell destruction if repair is unlikely.
Angiogenesis
The malignant cells grow into a small mass that develops nutrient-bearing blood vessels in a process called angiogenesis.

ENVIRONMENTAL DISEASE - Moore

How Does Cancer Develop?

Recently, anti-angiogenesis compounds have been developed that prevent or reverse the formation of blood vessels in tumors of rats.

ENVIRONMENTAL DISEASE - Moore

Major Cancer Risks

Smoking
Smoking cigarettes causes more than 30 percent of all cancers in the United States.
Eighty eight percent of the 120,000 people newly diagnosed with lung cancer each year are smokers.

ENVIRONMENTAL DISEASE - Moore

Major Cancer Risks

Diet
High fat intake has been linked with increased risks to colon and prostate cancer, while being excessively overweight encourages the growth of endometrial cancer.

ENVIRONMENTAL DISEASE - Moore

Major Cancer Risks

Diet
Cruciferous vegetables including broccoli, cabbage, cauliflower, kale, and brussel sprouts all produce a powerful isothiocyanate anti-carcinogen known as sulforaphane

ENVIRONMENTAL DISEASE - Moore

Major Cancer Risks

Diet
Apoptosis may be triggered by butryric acid produced when bacteria ferment fiber in the gut.
Consumption of high fiber foods instead of refined flour and processed foods also appears to reduce the risk of cancer.

ENVIRONMENTAL DISEASE - Moore

Trends in Cancer

Data show that after increasing for 1.2 percent annually from 1973 to 1990, the rate of new cases (incidence) of 23 major cancers sites combined fell an average of 0.7 percent a year from 1990 to 1995 (Fig. 4-13).

ENVIRONMENTAL DISEASE - Moore

Fig. 4-13a

Adapted from Wingo et al et al.. 36

ENVIRONMENTAL DISEASE - Moore

Trends in Cancer

NCI has reported that the rate of cancer among American children has been steadily rising nearly one percent per year.

ENVIRONMENTAL DISEASE - Moore

Trends in Cancer

Children tend to be more susceptible to environmental toxins because:
they take in more food, water, and air and accompanying carcinogens relative to body weight compared to adults;
nursing infants get higher exposures of substances such as dioxin in breast milk than adults exposed to background levels;

ENVIRONMENTAL DISEASE - Moore

Trends in Cancer

Children tend to be more susceptible to environmental toxins because:
children have a higher internal dose of toxins and greater genetic damage than adults who have similar exposures to tobacco smoke and polyaromatic hydrocarbons (PAH);

ENVIRONMENTAL DISEASE - Moore

Trends in Cancer

Children tend to be more susceptible to environmental toxins because:
children have reduced detoxification and repair systems;
they have a higher rate of cell proliferation during early developmental stages; and
children have increased absorption and retention of toxins.

ENVIRONMENTAL DISEASE - Moore