Human Carcinogens PDF

Human carcinogens  Clinical studies  Epidemiological studies  Experimental studies  Eventually all carcinogens lead to inheritable gene mutations that in most of the cases affect cell cycle or apoptosis NORMAL CELL...

Human carcinogens  Clinical studies  Epidemiological studies  Experimental studies  Eventually all carcinogens lead to inheritable gene mutations that in most of the cases affect cell cycle or apoptosis NORMAL CELL Acquired environmental Successful factors DNA repair DNA DAMAGE Unsuccessful Inherited mutations DNA repair MUTATED CELL Mutation of genes that control growth and division Inactivation of Activation of Inactivation of tumor genes that produce growth producing suppressor genes apoptosis genes (proto- oncogenes) Cell Proliferation Tumor Formation Chemical Carcinogens  Polycyclic hydrocarbons- scrotal cancer in chimney sweeps associated with soot. Produces problems at local site only.  Alkylating and acylating agents: direct DNA damage – also anticancer drugs o produce leukemia later on  Cigarette smoke- oral cancer, laryngeal cancer, lung cancer, bladder cancer, pancreatic cancer  Aromatic amines- produce problems at distant sites such as bladder  Cyclamates - some of the artificial sweeteners such as saccharin  Azodyes- usually occupational and produce bladder and liver cancer. " Butter yellow" was a food additive  Nitrosamines- may be associated with stomach cancer  Aflatoxin- naturally occurring carcinogen that is associated with hepatocellular carcinoma and is a toxin produced by a mold that grows on grain and peanuts, and all snuts and seed stored in humid conditions.  Betel nut- chewed in Sri Lanka and India and produces oral cancer. Dr M Hossu Notes 152   Safrole: sassafras oil, brown camphor oil, which is present, in small amounts, in anise, nutmeg, cinnamon, and black pepper.  Vinyl Chloride, Ni, Cr Physical carcinogens  U.V. radiation and skin cancer  X-ray radiation and leukemias and skin cancer in exposed skin  Radio-isotopes and what will affect the response such as how penetrating the particle is, how much energy it has and how much radiation the individual was exposed to. o Naturaly occurring: Uranium, Thorium , radon o E.g. radioactive iodine and thyroid cancer.  Nuclear fallout- particularly associated with leukemias and thyroid cancer if there is radioactive iodine in the fall out. Viral carcinogens  Oncogenic RNA viruses o HTLV-1- Human T cell Leukemia Virus only virus associated clearly with a human malignancy i.e. T cell leukemia o HTLV-3 (HIV) o Hepatitis C virus produces hepatocellular carcinoma  Oncogenic DNA viruses o Human papilloma virus (HPV)  Benign tumors we call warts or condylomas  Cancer of the uterine cervix o Epstein-Barr virus (EBV, HV-4)  Burkitt's lymphoma  Nasopharyngeal carcinoma in Chinese particularly o HHV-8 - Kaposi's sarcoma, particularly in patients with AIDS acquired by homosexual transmission o Hepatitis B virus (HBV)- Hepatocellular carcinoma in cases of a chronic virus infection of the liver Dr M Hossu Notes 153  Clinical manifestations of Neoplasia Local manifestations  Mass effect  Compression or erosion of normal tissue o Pancoast’s tumor  Pancoast’s syndrome-Erosion of lower trunk of brachial plexus  Horner’s syndrome-Sympathetic Chain Erosion o Obstruction of a tube o Superior Vena Cava Compression o Bronchial obstruction  Ulceration of a surface  Erosion of a blood vessel producing a hemorrhage Systemic effects o Fever o Anorexia and weight loss- Cachexia o Infections o Anemia Paraneoplastic syndromes  Endocrinopathies o Cushing’s syndrome produced by small cell carcinoma of the lungs, pancreatic carcinoma and neural tumors (ACTH like substances) o Inappropriate ADH secretion produced by small cell carcinoma of the lungs and intracranial neoplasms o Hypercalcemia produced by squamous cell carcinoma of the bronchus, breast carcinoma and renal carcinoma o Carcinoid syndrome produced by bronchial carcinoid tumors, gastrointestinal carcinoid tumors and pancreatic carcinoma o Polycythemia produced by renal carcinoma, hepatocellular carcinoma and cerebellar hemangioma  Nerve and Muscle syndromes o Myasthenia Gravis associated with tumors of the thymus gland o Myasthenic (Lambert-Eaton) syndrome associated with small cell carcinoma of the lungs (it improves with exercise) o Peripheral neuropathies associated with lung carcinomas and some others. o Cerebral and cerebellar degeneration associated with a number of different types of malignancy (lung, ovarian, breast, lymphoma) – Autoantibodies against proteins expressed by the tumor cross-react with glial and neural proteins o Dermatomyositis / polymyositis mediated by cytotoxic T cells with an (yet) unknown autoantigen; lung and bladder cancer, Non-Hodking lymphoma Dr M Hossu Notes 154   Osseous, articular, and soft tissues o Clubbing of the fingers & fingernails ↔DifDX: hypoxia (respiratory or cardiac) o Hypertrophic pulmonary osteoarthropathy associated with bronchogenic carcinoma  Hematologic o Venous thrombosis (Trousseau’s sign): associated with carcinoma of the pancreas and other malignancy o Non-bacterial thrombotic endocarditis: in many different advanced malignancies C Change in bowel or bladder habits A Anemia of unexplained cause U Unusual bleeding or discharge (breast, intestinal, cervical, uterine) T Thickening or lump in the breast or elsewhere I Indigestion or difficulty swallowing O Obvious changes in a wart or a mole or a sore that doesn’t heal N Nagging cough or hoarseness of the voice Dr M Hossu Notes 155