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.