Final Exam Flashcards
It is generally accepted that most known human cancers result from…
Exposure to environmental carginogens.
- Natural chemicals
- Man made chemicals
- Radiation (not a chemical)
- Viruses
Dr John Hill
(1761) Suggested that snuff (sniffing tobacco) caused cancer
Natural PAH
Sir Percival Pott
(1775) Chimney sweep and scrotal cancer
Natural PAH
Katsusabur Yamagiwa
(1915) Link between coal tar on the skin and skin cancers on rabbits.
Only 7/137 rabbits for tumors.
Frequency (every 2 or 3 days)
First direct demonstration of chemical carcinogens.
(natural PAH)
Genotoxicity
The study of adverse effects of physical and chemical agents on the genetic material of cells (DNA and chromosomes) and the subsequent expression of these changes
DNA review
- DNA is the genetic material that codes for all characteristics of life
- Made up of two strands of pentose sugar, phosphate group, and a nitrogenous base
- A to T
- C to G
- Chromosomes are groups of genes. Genes are groups of Proteins and enzymes. And those are groups of DNA.
RNA
Differences between DNA and RNA
- DNA codes for RNA
- Uracil replaces Thymine, so we have A,U,C,G
Makes codons
Nucleotides
In DNA (A,T,C,G) In RNA (A,U,C,G)
Made of pentose sugar, phosphate group, and nitrogenous base.
Codon
sequence of 3 nucleotides (A,U,C,G) that codes for an amino acid
Proteins / Enzyme
Chain of amino acids
Mutagenesis
the formation of mutations (loss, addition, or alteration of a small number of base pairs in DNA)
Carcinogenesis
the formation of tumors
Teratogenesis
the formation of developmental malformations
- (in utero exposures)
- (damages DNA)
Clastogenesis
loss, additon, or rearrangement of large parts of chromosomes.
Base pair
A to T (DNA)
C to G (DNA)
A to U (RNA)
Carcinogen vs Mutagen
Carcinogen causes cancer
- acts on proto-oncogene or tumor suppressor gene
Mutinagen does not
-can act anyhwere in DNA regardless of cell type
Where do carcinogens act?
Proto-oncogenes or tumor suppressor genes
Result - neoplastid growth
Mutagen
any chemical or agent that causes damage to the DNA or inhibits or damages DNA repair mechanisms.
Is the mutation damage inheritable?
It depends on
- which cells were damages.
- if the cells were repaired before passed on
Inheritablility of DNA damage in different cells
Germinal Cells (sex cells): yes it can be passed on
Somatic cells (anything besides sex cells): No, it cannot be passed on.
How many mutations happen in each mammal cell every day?
Several thousand mutations in the sequence of DNA
Most are corrected through repair mechanisms before cell replicates
Apoptosis
Programmed cell death.
If cell detects issue and cannot be repaired, it will commit suicide.
Tumor suppressor
Types of Mutations
Base-pair transofrmations: one base is replaced by another
Frameshift mutations: (very bad)
- Base-pair insertion
- Base-pair deletion
These are all point mutations
A mutation can result in..
- a protein with an incorrect amino acid that is still function
- protein that is not functional
- total DNA disruption, inability to grow and divide, and possibly cell death
- inherited defects in germ cells (gametes)
- developmental defects
- disruption of cellular organization (tumors)
How can toxicants damage DNA?
- Chemical Modification of base
- Deamination, removed NH2
- Alkylation, add CH3
- Covalently bind to a base to form an adduct
- Insertion of chemical into DNA
- Causing DNA strand to break
Double strand breakage
Chemical breaks both strands of DNA in the same spot
Adduct
A covalent attachment of a chemical compound to DNA.
Can block DNA synthesis, resulting in noncoding region.
Plays a key role in initiation, early promotion, and later stages of tumor progression.
How smoking causes cancer
- Incomplete combustion of organic matter
- Inhale PAHs
- Benzoapyrine
- Adduct to DNA,
- Can play a role in chemical carcinogenesis.
Where do adducts form? (PAHs)
- In DNA of ANY CELL
- PAH metabolites prefer to bind to guanine bases, bind to PURINES (adenine and guanine)
- Adducts most commonly found in LIVER
- Liver is where a lot of things are metabolized, so if the metabolites of PAHs are what are adducting to DNA, it makes sense that this is where they would be.
The Ames test
Usually Salmonella bacteria can produce its own histidine.
In the test, we mutate the Salmonella so it cannot make its own histidine.
Its plated on the agar plates.
We introduce a chemical to mutate it back to its ‘wild type’.
If the Salmonella is able to divide again, then the chemical has caused a mutation in the bacteria and the bacteria can create its own histidine.
We use the control to test if the mutation is because of chance mutation or due to the chemical introduced.
Problems with the Ames Test for testing for carcinogens
- Some chemicals must be metabolized before they are mutagens.
- Several steps must occur following a mutation for cancer to occur.
- Not all cancers are caused by mutation
- How applicable is bacterial mutation to mammals?
What do PCBs tell the DNA?
PCBs tell the DNA to start making enzymes.
How to get the metabolites from a mammal to use in the Ames Test
- Expose test animal to PCBs
- PCBs create enzymes
- Take liver out of test animal
- Get the enzymes from the liver
- Expose enzymes to chemicals to see if it mutates.
- Enzymes produce metabolites when exposed to chemicals.
- Expose bacteria to metabolites
Comet Assay
This test specializes in STRAND BREAKAGE
Can do this test with any organism
Expose organism to chemical. Chemical will or will not cause genotoxicity. Collect cells and get DNA out. Apply electricity, and this causes DNA to move.
BIG PIECES GO SLOWER THAN SMALLER PIECES.
Stain plate so we can see where the DNA has moved to.
How far did the pieces move? How many moved how far?
Neoplasm
A new and abnormal growth of tissue in some part of the body
Heritable damage (daughter cells get same mutation)
Relatively autonomous growth (cell will grow without regulation)
-Benign or malignant
Undifferentiated vs Differentiated
Differentiated - Liver cells, skin cells
Undifferentiated - stem cells.
Benign Neoplasm
- Remain differentiated (liver cells stay liver cells)
- does not metastasize because they are already differentiated
- slow growth
Malignant neoplasms
- Undifferentiated form (can start to invade other tissues, can grow in a new area)
- rapid growth
- metastasize: malignant cancerous cells break off original part of body and move, through circulatory and lymphatic systems, to other parts of the body and can spread cancer that way. The malignant cells can metastasize because they are undifferentiated
Hyperplasia
increase in the number of cells in tissue or organ,
the enlargement of an organ or tissue caused by an increase in the reproduction rate of its cells
-normal cells multiply (not a bad thing, like when you cut your finger)
Neoplastic hyperplasia
no longer responds properly to chemical signals telling the growth to stop.
A proto-oncogene
a gene that encodes for proteins that stimulate cell division
If a mutation overactivates stimatory proteins, coded by proto-oncogenes, it will cause the cell to proliferate excessively.
Mutates proto-oncogenes become cancer causing genes called oncogenes
Oncogenes
mutated proto-oncogenes that cause cancer
onco- greek for tumor
Tumor suppressor genes
a gene that encodes for proteins that stop cell division in a normal cell.
- inhibit abnormal growth
- often a point mutation in tumor suppressor genes
p53
Tumor suppressor gene that is the most commonly mutated
A gene that codes for a protein that regulates the cell cycle.
mutated in 53% of human cancers.
responsible for apoptosis
carcinogenesis
multistage process involving inappropriate activation of normal genes (proto-oncogenes) to become oncogenes
OR
inactivation of tumor supressor genes result in neoplasia.
Three stages of carcinogenesis
Initiation
Promotion
Progression
Initiators
cause a simple mutation in one or more cellular genes that control key regulatory pathways of the cell. (tumor suppressor or proto-oncogene)
They convert normal cells to latent tumor cells (has the ability to divide uncontrollably but are not yet)
cause structural changes in DNA
Promoters
enhance growth and continue expansion of latent tumor cells (now begins the uncontrollable growth)
Cause an altered expression of the genes but does not change the DNA
- asbestos
- hormones associated with hyperplasia
- saccharin
- a high caloric diet can cause cells to grow
cancer slope factor
hmm
germ cells
sex cells (ova or sperm)
- mutations of these cells can be passed on to offspring
somatic cells
all other cells besides germ cells
- mutations in these cells cannot be passed on to offspring
Intercalation
hmm
metastasize
malignant cancerous cells break off original part of body and move, through circulatory and lymphatic systems, to other parts of the body and can spread cancer that way. The malignant cells can metastasize because they are undifferentiated
How do we study Fate and Transport
hmm
Fate
where a chemical is ultimately stored in an environment
Behavior
how the chemical is transported through the environment
How do we model Fate and Transport
hmm
Persistence
A persistent chemical is one that has a half life (t1/2) greater than
- 2 months (water,soil,sed)
- 2 days (air)
How is persistence influenced? How can the persistent chemical be broken down?
Chemicals can be broken down by…
- UV light
- Water
- Microorganisms
Bio availability: What it is, what influences it? (3 factors, with examples)
Bio-availability: the degree to which the contaminant is free to be taken up and to cause an effect at the site of action or on an organism at a higher trophic level.
Where the chemical is in the environment affects its bio-availability
Dependent on
- Properties of the environment
- Properties of the chemical
- Properties of the organism
PBDEs
sources, effects, key features, mechanisms
dioxins
sources, effects, key features, mechanisms
oil pollution
sources, effects, key features, mechanisms
PAHs
sources, effects, key features, mechanisms
dispersants
sources, effects, key features, mechanisms
inorganic pollutants
sources, effects, key features, mechanisms
emerging chemicals
sources, effects, key features, mechanisms
PPCPs
sources, effects, key features, mechanisms