Download Environmental Health: sanitation, water, pesticide and - Wk 1-2

Environmental Health: sanitation, water, pesticide and industrial residues
1. Describe methods of exposure to environmental chemicals
Exposure to environmental chemicals can occur via:
 skin contact
 inhalation
 ingestion (food, water)
 eye contact
 vertical transmission (mother to child in breast milk, placental transmission)
2. Discuss, using examples, the potential for the environmental agents to impact
upon the cell cycle
Carcinogenesis
 two steps → initiation and promotion
 First Stage: Initiation→ irreversible and rapid process whereby a chemical
produces an irreversible change in the DNA of a target cell
 Second stage: Promotion → involves a series of reversible tissue and cellular
changes during the long latency period before the appearance of the first
autonomous cancer cell
 Progression → stepwise evolution of cancer cells as they become progressively
more malignant (growing rapidly and unable to repair defects)
Initiation of Carcinogenesis
Carcinogens fall into one of two categories:
1. Direct acting carcinogens: do not require chemical transformation for their
carcinogenicity.
2. Indirect acting carcinogens/procarcinogens: require metabolic conversion in vivo
to produce ultimate carcinogens capable of transforming cells.
Molecular targets of chemical carcinogens
 Malignant transformation results usually from mutations that affect oncogenes,
tumour suppressor genes and genes that regulate apoptosis
 DNA is a primary target for chemical carcinogens, but there is no single alteration
that can be associated with initiation of chemical carcinogenesis.
 Each class of carcinogens tends to produce a limited pattern of DNA damage.
Thus, the presence of certain types of DNA damage in human tumours can
provide molecular cues to their causation.
 Although any gene could be targeted, the ras and p53 genes are commonly
involved
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p53 is a tumour suppressor gene that arrests cells in the G1/S phase of the cell
cycle if there is DNA damage and induces apoptosis is the damage is too severe
to be repaired
ras is an oncogene (see Nic’s notes)
malignant cells posses the ability to bypass the restriction on entrance into S
phase normally imposed by damaged DNA
this allows the cell to accumulate genetic changes and promotes the selective
outgrowth of cells with a proliferative advantage
most chemical carcinogens act by producing changes in DNA (initiation phase of
carcinogenesis)
Radiation
 direct effects on DNA or activation of oncogenes
Aflatoxin (from fungus in improperly stored food)
 oxidized in the liver to a carcinogen that binds with guanine in DNA of hepatic
cells
Cigarette Smoking
 cigarette smoke contains numerous carcinogens
 most important is probably polycyclic hydrocarbons (tar)
 these are direct acting carcinogens on the skin, but are procarcinogens in lung
and bladder cancer
 inhaled polycyclic hydrocarbons → converted in liver to an epoxide by a
microsomal enzyme (aryl hydrocarbon hydroxylase)
 the epoxide (the ultimate carcinogen) combines with guanine in DNA leading to
neoplastic transformation
UV radiation
 causes linkages between pyrimidine bases on DNA
3. List examples of environmental carcinogens and mutagens
Carcinogens are substances that are known to cause cancer or at least produce an
increased incidence of cancer in a population.
Mutagens are physical or chemical agents that change the genetic material of an
organism and thus increase the frequency of mutations above the natural background
level. As many mutations cause cancer, mutagens are typically also carcinogens.
Chemical
polycyclic hydrocarbons
 soot

inhalation or chewing of
tobacco products
Aromatic Amines
 benzidine, 2naphthylamine
Aflatoxins
Nitrosamines
Cancer therapeutic agents
 Alkylating agents
(cyclophosphamide,
chlorambucil, thiotepa,
busulfan)
Asbestos
Source
chimneys, air
pollution
skin; scrotal cancer in
chimney sweeps
mainly cigarettes
lung, bladder, oral cavity,
larynx, oesophagus
first recognized in
workers of the
leather dye
industries
produced by the
fungus Aspergillus
flavus which grows
on improperly
stored food
conversion of
nitrities in the
stomach (nitrites
are ubiquitous in
food because of
their common use
as preservatives)
Vinyl Chloride
bladder
liver
? oesophagus, ? stomach
leukaemias
has been used as
insulation material
and fire retardant
Alcohol
Heavy Metals
 nickel, chromium,
cadmium
 arsenic
Types of Cancer
lung, mesothelioma
mouth, pharynx, larynx,
oesophagus and liver
miners
lung
agricultural workers
exposed to arsenic
containing
pesticides
skin
gas used in PVC
manufacture
liver (angiosarcoma)
Radiation
Ultraviolet
Source
solar
X-ray
radiation therapy
diagnostic
Radioisoptopes
Types of cancer
skin (especially in fair
people)
malignant-neoplasms
(often sarcomas) 10-15
years later
dose believed to be too
small to cause harm
lung
occupational exposure in
mines
radioactive iodine therapy
increased cancer risk 15-25
(non-neoplastic thyroid
years later
disease)
Nuclear Fallout
Hiroshima, Nagasaki,
several kinds of cancers
Marshall Islands, Chernobyl
*’man made’ radiation however accounts for less than 1% of total radiation exposure of
the population. Most comes from the earth, rocks and cosmic radiation (i.e.
unavoidable background radiation)
Virus
Hapatitis B
Human papillomavirus
Epstein-Barr virus
Type of cancer
liver
cervix
nasopharynx, Hodgkin’s bdisease, Burkitt’s
Lymphoma