Slide 1 - Dr. Jennifer Staiger
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Transcript Slide 1 - Dr. Jennifer Staiger
Chemicals and Cancer
Aniline Dye and Cancer
Extraction of aniline
from Coal was the
beginning of the aniline
dye industry.
Later 2-naphthylamine
was used as the starting
material for this process.
Factory workers
developed bladder
cancer.
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Chemical Carcinogenesis
Principle of Chemically
induced Carcinogenesis:
Long Delay
Dose Dependence
Organ specificity
Examples of Chemical
Carcinogenesis
Asbestos and Mesothelioma
Pesticide, ethylene dibromide
(EDB)
Dioxin
Asbestos and Mesothelioma
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Industrial Pollution and Cancer
Low doses of carcinogens
released into the
environment.
Cancer risk is related to
cancer dose.
Historical trends do not
support the argument for
industrial pollution.
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Low Dose Environmental Pollution
The epidemiological
approach is not sensitive
enough to detect small
increased in cancer risk.
Limitations of Animal
Models in assessing low
dose carcinogen exposure
Maximum Tolerated Dose
Threshold
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
High and Low Dose Cancer Risk
Linear Model
Threshold Model
Hormetic Model
Extrapolation of animal
Data
Known human
carcinogens
Reasonable anticipated
human carcinogens
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Categories of Chemical Carcinogens
From L. J. Kleinsmith,
Principles of Cancer Biology.
Copyright (c) 2006 Pearson
Benjamin Cummings.
Chemical Carcinogens
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Electrophillic Carcinogens
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Electrophillic Carcinogens
Benzo[a]pyrene is activated to have
an epoxide group.
DNA-carcinogen complexes are
called DNA adducts.
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin
Cummings.
Site of DNA Adduct Formation
From L. J. Kleinsmith,
Principles of Cancer Biology.
Copyright (c) 2006 Pearson
Benjamin Cummings.
Carcinogens and DNA Damage
From L. J. Kleinsmith, Principles of
Cancer Biology. Copyright (c) 2006
Pearson Benjamin Cummings.
Chemical Carcinogenesis
Chemical carcinogenesis
is a multistep process.
Rous observed that
repeated application of
tar caused tumors in
rabbits.
There are two main steps
Tumor initiation
Tumor Promotion
From L. J. Kleinsmith, Principles of
Cancer Biology. Copyright (c) 2006
Pearson Benjamin Cummings.
Tumor Initiation
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Tumor Promotion
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
TPA and Tumor Promotion
From L. J. Kleinsmith, Principles of
Cancer Biology. Copyright (c) 2006
Pearson Benjamin Cummings.
Main Stages of Carcinogenesis
From L. J. Kleinsmith, Principles of
Cancer Biology. Copyright (c) 2006
Pearson Benjamin Cummings.
Transplantation of Cancer Nuclei
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Carcinogenic Potential
Incomplete
Carcinogens
Complete Carcinogens
Cancer Potency is
influenced by
Activation reactions
Electrophillic stength
of carcinogens
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.
Random Nature of Cancer
Potency and Dose of carcinogens
Random occurrence of mutations
Genetic risk factors contribute to acquisition and
progression of cancer.
Immunosuppressive drugs contribute to cancer
development.