Carcinogens

Henni vanda
 About this template
Definition

CARCINOGEN CARCINOGENESIS
Any substances that promotes ❑ The formation of cancer; normal cells are
carcinogenesis transformed into cancer cells.
❑ A multi steps process, cells undergo
profound metabolic and behavioral
changes,
❑ Proliferate in an excessive and untimely
way to escape surveillance by the immune
system,
❑ Invade distant tissues to form metastases
 Progression of cancer

▪ Many cancers arise from just one cell (or from a small number of cells).
▪ To become cancerous, this cell must acquire several changes in oncogenes
and tumor suppressor genes that will make the cell capable of proliferating
well beyond its normal limit.
▪ Mutation in DNA will disrupt the regulation process.
▪ DNA damage will cause changes in the physiological processes of DNA
replication and repair.
▪ Each time a cell divides, it has to produce a perfectly accurate copy of the 3
billion base pairs of its DNA. This process is tightly controlled by very
elaborate DNA proofreading and repair systems. However, errors may occur
and remain unrepaired.
 Three Fundamental Rules for Carcinogenesis

1. Cells divide only when receive appropriate signals. But in cancer cells,
they have to permanently activate cell division. The signals to stop division
is not recognized.
2. When confronted by stressful or improper conditions for DNA replication,
cells activate self destruction program, rather than allow DNA replication to
proceed in conditions where genes may become damage. In cancer cells,
the auto-destructing program is turned off. Master genes responsible for
this process are RB1 (also called the Retinoblastoma gene) and TP53 (which
produces the p53 protein, a stress sensor that normally prevents cells from
dividing when their environment is disturbed).
3. Normal cells divide only a limited, fixed number of times. Cells have a
“division counter” that prevents them from replicating their DNA beyond a
certain, predefined number of rounds. In the cancer cell, the activation of an
enzyme called telomerase allows the addition of new repeats at the end of
chromosomes, thus allowing the cell to divide well past the finite number of
divisions it has been programmed to make.
 Carcinogenesis Stages

A. Initiation → alteration or mutation of genes induced by

carcinogen, or spontaneously. Resulted in dysregulation of
biochemical signaling pathways associated with cellular
proliferation, survival, and differentiation, which can be
influenced by a number of factors, including the rate and type
of carcinogenic metabolism and the response of the DNA
repair function.
B. Promotion → relatively lengthy and reversible process.
Proliferating pre-neoplastic cells accumulate. Within this
period, the process can be altered by chemopreventive agents
and affect growth rates.
C. Progression is the final stage of neoplastic
transformation. Genetic and phenotypic changes and cell
proliferation occur.
 Carcinogenesis Stages

◉ This involves a fast increase in the tumor size, where the cells
may undergo further mutations with invasive and metastatic
potential.

D. Metastasis → the spread of cancer cells from the primary site to

other parts of the body through the bloodstream or the lymph
system.

Chemo-preventive agents are known to inhibit angiogenesis and

invasion of primary tumors, and thus could be utilized to inhibit the
metastasis of cancer.
OLIVEIRA, Paula A. et al. Chemical carcinogenesis. An. Acad.
Bras. Ciênc. [online]. 2007, vol.79, n.4 [cited 2019-03-26],
pp.593-616.
 Carcinogen

◉ Changes in genetic material can be inherited or can be due to

outside exposures (environmental factors).

Environmental factors including:

◉ Lifestyle factors (nutrition, tobacco use, physical activity, etc.)
◉ Naturally occurring exposures (ultraviolet light, radon gas,
infectious agents, etc.)
◉ Medical treatments (radiation and medicines including
chemotherapy, hormone drugs, drugs that suppress the
immune system, etc.)
◉ Workplace exposures
◉ Household exposures
◉ Pollution
 “
CARCINOGEN

* Genotoxic carcinogen → a chemical capable of

producing cancer by directly altering the genetic
material of target cells

* Non-genotoxic carcinogen → a chemical

capable of producing cancer by some secondary
mechanism not related to direct gene damage.
 Chemicals carcinogen

◉ Polycyclyc aromatic hydrocarbon (PAH) → benzopyrene, benzene,

nitrosamin.
From tobacco smoke, vehicle, and other smokes (fried or smoked meat
using charcoal and unhealthy oil).
◉ Acrylamid → from overheated carbohydrate foods (french fries, chips).
◉ Nitrosamine → from nitrites or nitrates in food preservatives (sausage).
Also produced during roasting/grilling food.
◉ Aromatic amines → butter yellow, tobacco smoke.
Naphthylamine, benzidine (dye substances), 3-acetylaminofluerene ,
chlornaphazine (drug for Hodgkin’s disease, causing bladder cancer).
◉ Alkylating agents → epoxide, lactone, nitrogen mustard. (gas) ,
Including chlorambucil and busulphan (depress all blood elements) will
trigger leukemia, cyclophosphamide triggers bladder cancer.
 Chemicals carcinogen

◉ Aflatoxin B1 → from Aspergillus flavus → liver

cancer
◉ Chromium (Cr), Nickel (Ni), and Uranium (Ur)
→lungs cancer
◉ Cadmium → prostate cancer
◉ Vinyl chloride → from polyvinyl chloride (PVC),
chemicals to produces plastics → angiosarcoma,
lung cancer, brain cancer, and leukemia.
 You can also split your content
Carcinogen

Carbon tetrachloride Hydrocarbonchloride

In plastic industry and dry- Chemicals in pesticide,
clean laundry can cause including eldrin and
angiosarcoma. dieldrin will cause
angiosarcoma.
Thiourea (textile industry)
and urethane (foam Saccharin, aspartame,
sponge) are carcinogen. and Cyclamat → artificial
sweetener → can promote
bladder and pancreas
cancer.
◉ Some food coloring is ◉ Chlornaphazine →
also carcinogen drug to treat hodgkin
◉ Phenacetin disease → also cause
(acetophenetidin) is a bladder cancer.
pain relieving and ◉ Dietylstilbestrol →
fever-reducing drug synthetic estrogen can
(analgesic), also cause endometrium
carcinogen → pelvic cancer.
and bladder cancer. It ◉ Phorbol ester → from
is banned since 1983. Euphorbiaceae → skin
cancer, liver, and lung
cancer
◉ Formaldehyde →medical laboratories and mortuaries as a
preservative, also widely used to make resins for household
items such as composite wood products, paper product
coatings, plastics, synthetic fibers and textile finishes.
◉ Aristolochic acids → a family of acids that occur naturally in
some plant species.
◉ Captafol → a fungicide that had been used to control fungal
diseases in fruits, vegetables, ornamental plants, and grasses,
and as a seed treatment. It has been banned in the United
States since 1999, but past exposures may still have an effect on
health.
◉ Certain inhalable glass wool fibers →include only those fibers
that can enter the respiratory tract, are highly durable, and are
biopersistent, they remain in the lungs for long periods of time.
The largest use of general purpose glass wool is for home and
building insulation, which appears to be less durable and less
biopersistent, and so less likely to cause cancer in humans.

◉ o-nitrotoluene → used as an intermediate in the preparation of

azo dyes and other dyes, including magenta and various sulfur
dyes for cotton, wool, silk, leather and paper; it is also used in
preparing agricultural chemicals, rubber chemicals, pesticides,
petrochemicals, pharmaceuticals and explosives
◉ Styrene → a synthetic chemical used worldwide in the
manufacture of products such as rubber, plastic, insulation,
fiberglass, pipes, automobile parts, food containers and carpet
backing. People may be exposed to it by breathing indoor air
with styrene vapors from building materials, tobacco smoke and
other products. The greatest exposure to styrene in the general
population is through cigarette smoking.

◉ Riddelliine → found in certain plants of the genus Senecio, a

member of the daisy family, grown in sandy areas in the western
United States and other parts of the world. Though not used
commercially in the United States, many species have been
identified in herbal medicines and teas.
◉ Potassium bromate (KBrO3)
◉ An oxidizing agent that has been used as a food
additive, mainly in the bread-making process.
◉ carcinogenic in rats and nephrotoxic in both man and
experimental animals when given orally.
◉ KBrO3 induces renal cell tumors, mesotheliomas of
the peritoneum, and follicular cell tumors of the
thyroid.
◉ KBrO3 is a complete carcinogen, possessing both
initiating and promoting activities for rat renal
tumorigenesis
Radiation
 In twoRadiation
or three columns

X-ray Radioactive Compounds Radon (Rn)

Dangerous for foetus. • Radium (Ra) found in Colorless, tasteless,
uranium, isotop of Ra is odorless gas, from
mesothorium (228Ra), uranium containing
Nuclear radiation
• Phosporus (32P), used minerals, usually
contained x-ray →
in radiolabelling for found in buildings and
cause cancer in short
DNA and RNA homes → cause lung
term; → cause
• Thorotrast → cancer for non-
hereditary mutation for
radiocontrast agent in smokers.
long term.
radiography
• All these substances
can cause
angiosarcoma,
osteosarcoma,
leukemia.
 Ultraviolet Radiation

◉ Three types of ultraviolet:

◉ UV A : Penetrates deep into the skin, will ages the skin.
◉ UV B: responsible for sunburns
◉ UV C: most dangerous, blocked by ozone layers, doesn’t reach earth’s
surface
◉ Too much UV radiation will damage DNA in the skin cells and will
trigger cancer.
◉ Types of skin cancer: squamous sarcoma, basal cell carcinoma, and
melanoma.
◉ More than 75% skin cancer is basal cell carcinoma → face and neck
◉ Squamous sarcoma → lips
Virus Carcinogen
 Virus carcinogens

❑Virus can cause genomic instability,

including accumulation of mutations,
aberrations and DNA damage.
❑DNA oncogenic viruses encode
oncogenes that transform infected
cells, frequently by targeting p53 and
pRB.
❑In addition, integration of viral DNA
into the genome can also play an
important role in promoting tumor
development for several viruses
 Virus carcinogens

◉ DNA damage can be caused by both endogenous and exogenous

factors, including inflammation induced by either the virus itself or by
co-infections with other agents, environmental agents and other
factors.
◉ Cancer develops years to decades following the initial infection.
◉ Viruses that have been linked to carcinogenesis include several DNA
viruses including:
1. Kaposi’s sarcoma herpesvirus (KSHV) →
_ Kaposi’s sarcoma, primary
effusion lymphoma
2. Merke cell polyomavirus (MCV) → skin cancer, especially to old people
3. Epstein-Barr virus (EBV) → Burkitt’s lymphoma and nasopharyngeal
carcinoma
 Virus carcinogens

4. Human papillomavirus (HPV) → cervical cancer, penile cancers

and some other anogenital and head and neck cancers
5. Hepatitis B virus (HBV) → hepatocellular carcinoma (HCC)
6. The simian virus 40 (SV40) → brain tumor, osteosarcoma,
mesothelioma (cancer caused by asbestos)

◉ RNA viruses:
1. Human T-lymphotropic virus-1 (HTLV-1) → leukemia
2. Hepatitis C virus (HCV) → hepatocellular carcinoma (HCC) and
possibly some lymphomas.
 “
◉ Parasites carcinogen
 Schistosoma haemotobium

◉ Cause carcinoma of the urinary bladder, the most

common malignancy in the Middle East and parts
of Africa where schistosomiasis is a widespread
problem
◉ N-nitroso compounds appear at high levels in the
urine of patients with schistosomiasis-associated
bladder cancer
 Clonorchis sinensis

◉ Known as Chinese liver fluke

◉ This parasite lives in the liver of humans, mainly
found in the common bile duct and gall bladder
◉ The infection, called clonorchiasis, generally appears
as jaundice, indigestion, biliary inflammation, bile duct
obstruction, even liver cirrhosis, cholangiocarcinoma,
and hepatic carcinoma
◉ Definite cancer-causing agent in the liver (carcinoma)
and bile duct (cholangiocarcinoma)
◉ group 1 biological carcinogen
 Opisthorchis vivarium

◉ Known as Southeast Asian liver fluke

◉ A food-borne trematode parasite from the family
Opisthorchiidae that infects the bile duct.
◉ People are infected after eating raw or
undercooked fish.
◉ Infection with the parasite is called
opisthorchiasis.
◉ O. viverrini infection also increases the risk of
cholangiocarcinoma, a cancer of the bile ducts.
 Thanks!

ANY QUESTIONS?