SOPH 352 Carcinogens and Co-carcinogens_jjato_2024.pptx

CARCINOGENS & CO-CARCINOGENS SOPH 352 PHYTOPHARMACEUTICALS & POISONS J JATO PCOGNOSY & HERB. MED. SOP, UHAS, PMB 31, HO  Course content 1. Lower and Higher Poisonous Plants: Local and Foreign Sources 2...

CARCINOGENS & CO-CARCINOGENS SOPH 352 PHYTOPHARMACEUTICALS & POISONS J JATO PCOGNOSY & HERB. MED. SOP, UHAS, PMB 31, HO  Course content 1. Lower and Higher Poisonous Plants: Local and Foreign Sources 2. Natural Hallucinogens 3. Natural Allergens 4. Carcinogens and Co-carcinogens 5. Anticancer Agents 6. Teratogens 7. Venoms, Stings and Antidotes 8. Pests and Pest Control 9. Antioxidants 10.Marine drugs 11.Nutrition and Health, including Vitamins and Minerals (Nutraceuticals) 2  Course Objectives By the end of this session students should be able to:  classify various types of dangerous plants  identify some common poisonous plants  explain the hazards associated with dangerous plants  advise the public on dangerous plants  identify common nutraceuticals 3  Carcinogens & Co-Carcinogens Introduction Definitions pictogram for Mechanism Carcinogens mutagens repro-toxic substances Toxicology Carcinogens  Introduction Cancer: An abnormal or uncontrolled growth of new cells in any part of the body, characterized by cells that tend to invade surrounding tissue and metastasize to new body sites. Cancer = unrestrained cellular proliferation For this, different steps are necessary: Initiation: DNA damage occurs, leading to abnormal cell growth. Promotion: Factors like cell division acceleration contribute to tumor formation. Progression: Cancer cells invade surrounding tissues and may spread. Malignancy: Uncontrolled growth and potential harm to organs Examples of cancers – Breast cancer, lung cancer, colon cancer, skin cancer,...  Introduction - carcinogens Carcinogen: Any substance that can cause cancer. can be biological, physical, or chemical in nature May have not immediate apparent harmful effects Chronic toxins & cause damage after repeated/long-term exposure Any discrete chemical compound which has been shown to cause cancer in human or animal studies. – Many are commonly used in laboratory operations, shops and art studios. Examples of products causing cancer? – Benzene, asbest, cigarette smoke, food, ethylene oxide, chromium VI, toluene, …  Definitions Mutagen: – Substance that can damage the hereditary material (DNA) – Mutagen may cause cancer, but not always – Most, but not all, carcinogens are mutagens – Can be a chemical substance, a virus, ionizing radiation – have adverse effects on fertility and general reproductive performance Teratogens – act during pregnancy to cause adverse effects on the embryo or fetus including malformations, retarded growth and postnatal deficiencies. – Reproductive toxins can affect both men and women.  Definitions Co-carcinogens: – a chemical substance that promotes the effects of a carcinogen – Not carcinogenic itself, but can increase the carcinogenic effects of a known carcinogen when the two substances are present together – E.g. diterpenes: esters of phorbol, daphnane & ingenol – promutagens and procarcinogens Procarcinogens – A chemical substance that becomes a carcinogen only after it is altered by metabolic processes (liver metabolism) Promutagens – a chemical that is not mutagenic in itself, but can be biologically transformed into a mutagen Carcinogenic Materials Asbestos Certain chemicals Coal tars & coke oven emissions Hardwood sawdust (certain species) Ionizing radiation Natural products (progesterone, safrole) Tobacco smoke Ultraviolet radiation Synthetic dyes  Route of Entry for Carcinogens ‘All substances are poisons, there is none which is not a poison. The right dose differentiates a poison and a remedy’ - Paracelsus Routes Inhalation -Breathing gases, fumes and vapors is the most common form of exposure. Ingestion - Swallowing of a carcinogen. Skin absorption - many solvents and other chemicals go directly through the skin. End points: Respiratory system; lungs Blood Digestive system; intestines Liver Skin Kidney Bones Reproductive system Cancers & Implicated Carcinogens Lung membrane cancer (mesothelioom) - Asbestos Cancer nose - Tropical hardwood Leukaemia - Benzene, ionizing radiation Bladder cancer - Aniline industry – dyes Mostly avoidable causes  Classification of Carcinogens 1 Carcinogenic to humans Sufficient evidence 2A Probably carcinogenic to Limited indication humans 2B Possibly carcinogenic to Insufficient indication in humans lab situations 3 Not classifiable as Limited indication in carcinogenic to humans animal surveys 4 Probably not carcinogenic to Indication for absence of humans carcinogenicity  Chemical Classes of Carcinogenic Compounds  Epoxides: Ethylene  N-Nitroso compounds: oxide Propylene oxide N-nitrosodimethylamine  Organohalogens Vinyl chloride Carbon  Aromatic Amines: tetrachloride Chloroform Benzidine Hexachlorobenzene Aniline Trichloroethylene o-Anisidine  Hydrazines: o-Toluidine Hydrazine (and salts)  Aromatic hydrocarbons: 1,2 Dimethylhydrazine Benzene Benz[a]anthracene Benzo[a]pyrene 13  Chemical Classes of Carcinogenic Compounds  Misc. organic compounds:  Misc. inorganic comp.:  Formaldehyde  Arsenic & its cpds  Acetaldehyde  Chromium & its cpds  1,4-Dioxane  Thorium dioxide  Ethyl carbamate  Beryllium & its cpds  2-Nitropropane  Cadmium & its cpds  Styrene  Thiourea  Lead & its cpds  Thioacetamide  Nickel & its cpds  Selenium sulfide 14  Carcinogens The effect may not occur at time of exposure By the time it occurs the person may not be working with the substance (latency time) People vary in susceptibility (react differently) age, gender, health status,... Complications of combined effects Exposure to different substances Exposure to alcohol, tobacco or prescribed drugs (e.g. synergistic effects asbestos and tobacco) Impact of lifestyle Detailed toxicological information is often not available for many substances  Plant carcinogens & co-carcinogens Carcinogens – Pyrrolizidine alkaloids (Symphytum spp., Petasites hybridus, Alkanna tinctoria, Tussilago farfara, Eupatorium cannabinum) – Anthranoid drugs (aloes) – Furanocoumarins (psoralens) – 2-Naphthylamine (Nicotiana tabacum) Co-carcinogens – Diterpenes (esters of the phorbol and ingenol) – Croton tiglium seed oil 16  References 1. Evans, W. C., Evans D. Trease and Evans' Pharmacognosy, W B Saunders, Philadelphia, 2009 ISBN: 9780702029332 2. Heinrich, M., Barnes, J., Gibbons, S. and Williamson, E. M. Fundamentals of Pharmacognosy and Phytotherapy, Churchill Livingstone, Edinburgh. 2004 ISBN: 978-0443071324 3. Nelson L. S., Shih R. D., Balick, M. J. Handbook of Poisonous and Injurious Plants, Second Edition: Springer, 2007 ISBN: 0387312684, 978-0387312682 4. Frohne D., Pfander H. J., McKinney P. (Eds) Poisonous Plants: A Handbook for Doctors, Pharmacists, Toxicologists, Biologists and Veterinarians Second Edition Manson Publishing, 2005 ISBN: 9781874545941