Cancer: cancrum ( ), A malignant neoplasm Tumor--- ---Any swelling or mass of tissue occupying a volume of space Neoplasm--- ---A A heritably altered, relatively autonomous growth of tissue Multistage Chemical Carcinogenesis M Introduction to DNA and Genes
IARC classification of animal and human carcinogens
Proportions of cancer deaths attributed to various environmental factors. Polycyclic aromatic hydrocarbons (PAHs( PAHs) A pyrolysis products of oils and biological materials but also generated in tobacco, whisky, grilled meat and by incomplete combustion of fossil fuels such as coal and petrol. The parent compound is phenanthrene,, composed of three fused aromatic (benzene ring) PAHs form adducts only after enzyme activation The minimum requirement for carcinogenicity Three fused aromatic rings in the phenanthrene figure Additional fused rings And/or a methyl group in the bay ring Carcinogenic potency of polycyclic aromatic hydrocarbons. Aromatic amines Bladder cancer: 2-naphthylamine 2 in dyestuff and rubber industry Butter yellow used to color margarine in the 1930s. It was withdrawn from use when shown to cause liver and bladder cancer in animals. -- 10-120 µg -- 0.32-20 µg -- : 17 µg US NRC Acs Monograph 182, Vol. 1, pp 829-868, 1984
Nitrosamine ( ) 1. (Nitrosamine) 2. 3. 4. 5. Vinyl chloride used in the plastic industry (PVC) for products such as food wrappers Vinyl chloride causes hepatic angiosarcoma ( ) C C GSH GSH GSH: Glutathione 135 210 (cogeners)
210 >700 o C TEQ 1-6 pg/g 7-20 pg/g 1-60 pg/g 0.002-0.02 pg/m 3 0.02-0.2 pg/m 3 0.00056 pg/l? (2003-2004) 2004) PCDDs/F /F Food PCDDs/Fs Unit 1.840 pg WHO-TEQ/g lipid 0.609 pg WHO-TEQ/g lipid 0.460 pg WHO-TEQ/g lipid 0.728 pg WHO-TEQ/g lipid feeds Modified from: http://www.deh.gov.au/industry/chemicals/dioxins/factsheet3.html Australia, National Dioxins Program Fact Sheets. Figure 1. Sources and pathways of dioxins
(tolerable intakes) guidance values WHO (1998) TDI 1-41 4 pg WHO TEQ/kg bw/day ( ) EU SCF (2001) TWI 14 pg WHO TEQ/kg bw/week UK COT (2001) TDI 2 pg WHO TEQ/kg bw/day JECFA (2001) PTMI 70 pg WHO TEQ/kg bw/month Provisional tolerable monthly intake for PCDDs, PCDFs,, & coplanar PCBs (by the Joint FAO/WHO Expert Committee on Food Additives) Lipid Peroxidation Phospholipids (membranes) amphipathic affects access Hydrophilic Head Hydrophobic Interior Hydrophilic Head (i) i) (Initiation) Polyunsaturated fatty acids more susceptible RH O R 2 (ii) (Propagation) R O ROO ROO 2 (DNA RNA) RNA) ROO RH ROOH ROOHR Peroxidation occurs in three stages: Initiation Propagation Termination (ii)
( ) ( ) (Phytochemicals) (Flavonoids) (Indoles) (genistein) (Lycopene) The longer one lives the more likely one is to get cancer? Fig.1.1 Influence of age on cancer incidence (age,lifestyle) Multi-step mechanism Carcinogene sis requires several cellular changes. The poorer, the riskier.
How rich is rich enough?
(risk assessment) assessment Assessment Evaluation What is risk? (definition of risk)
Where does risk originate from? Opportunity Risk (population) (uncertainty) (probability distribution) unequal distribution risk-takers are not the beneficiary involuntary risk
: The Benchmark dose model
Is risk assessment a fortunate-teller? Is risk assessment a fortunate-teller? How accurate is accurate enough? Precaution principles
Model showing how information about benefit or information about risk AFFECT AFFECT Slovic P, 1999. AFFECT Information Inference Information Inference benefit is high risk is low benefit is low risk is high AFFECT Information Inference Information Inference risk is high benefit is low risk is low benefit is high Health risks to the parents (n=1081) Violence Power lines Nuclear waste Traffic accident Cigarette Smoking Flood Free pan Chemical Industry Ozone depletion Drinking alcohol Outdoor air pollution PCBs and Dioxin Typhoon Bacteria in food Thermal power station Motor vehicle accidents Non-Rx drugs Noise Indoor air pollution Malnutrition Cross railroad Suntan Asbestos Trash disposition Roasted food Taking airplane Waste incinerators Medic X-ray Stress Contraceptive pills Contact lenses Watching TV Climate changes Terminals Canned food Bottled water Xerox machine Play basketball Rx drugs high risk moderate risk slight risk no risk don't know Cigarette smoking Motor vehicle accidents Health risks to the experts (n=150) Stress Suntan Ozone depletion Drinking alcohol Asbestos Nuclear waste PCBs and Dioxin Bacteria in food Malnutrition Medic X-ray Climate change Indoor air pollution Rx drugs Waste incinerators Non-Rx drugs Power lines Outdoor air pollution Violence Chemical industry Contraceptive pills Bottled water Tap water high risk moderate risk silent risk no risk don't know Ulrich Beck