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Chemicals and Cancer. From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Aniline Dye and Cancer Extraction.

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Presentation on theme: "Chemicals and Cancer. From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Aniline Dye and Cancer Extraction."— Presentation transcript:

1 Chemicals and Cancer

2 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. 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.

3 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

4 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Asbestos and Mesothelioma

5 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.

6 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

7 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

8 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Categories of Chemical Carcinogens

9 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Chemical Carcinogens

10 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Electrophillic Carcinogens

11 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.

12 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Site of DNA Adduct Formation

13 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Carcinogens and DNA Damage

14 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

15 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Tumor Initiation

16 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Tumor Promotion

17 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. TPA and Tumor Promotion

18 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Main Stages of Carcinogenesis

19 From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Transplantation of Cancer Nuclei

20 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

21 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.


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