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Transcript
You Are What You Eat CH339K Life Rule 1: Nobody gets out alive Cover of Science, Sept. 23, 1983 Mutagens and Carcinogens • Mutagens cause mutations in the DNA genome • Carcinogens increase the cancer rate in a given organism • Vast majority of carcinogens are mutagens • Not all mutagens are necessarily carcinogenic • Carcinogenesis analysis requires animal studies • Mutagens can be detected more simply and much less expensively • Restrict carcinogenesis testing to known mutagens Finding Mutagens – the Ames Test • Named for Bruce Ames, at UC Berkely • Uses Salmonella typhimurium that has defective histidine anabolism • Strains are used with both point mutations and frameshift mutations in histidine synthesis genes • Rat liver extracts are added to the chemical being studied to mimic bodily metabolism • BECAUSE the actual mutagen may not be the chemical itself, but a metabolic product Things we put into our food • Cooking your meat over open flame or in a smoker (or using liquid smoke) produces polyaromatic hydrocarbons (PAHs) • Cooking your meat over open flame or in a smoker (or using liquid smoke) produces polyaromatic hydrocarbons (PAHs) • Benzo(A)pyrene is metabolized to benzo[a]pyrene-7,8-diol-9,10-epoxide Mutagenic action • Benzo(a)pyrene and its epoxide are intercalators • Intercalating agents stack between the bases of a DNA double helix • The epoxide also formas a covalent bond with G residues at N2 • Helix distortion causes copy errors – mostly frameshifts Heterocyclic amines • Produced in cooked meat and fish from amino acids, sugars, and creatine HAs • mice tumors developed in the liver , forestomach, lung, blood vessels, hematopoietic system, and lymphoid tissue HAs (cont.) Heterocyclic amines “Standard” carcinogens HAs – Metabolic activation Natural Pesticides • • • • • • Safrole Aflatoxins Psoralens Solanines Pyrollizidines Others Safrole • • • • • • Sassafras oil Banned in USA from foods and skin products Formerly an ingredient of “natural” root beers Metabolized to 1-hydroxysafrole Binds to both DNA and proteins Induces liver tumors Aflatoxins Aflatoxin b1 • Produced by Aspergillus molds • Common contaminant of corn, grain, nuts, peanut butter, bread, cheese, fruit, and apple juice • Paricularly concentrated in organic peanut butter • Both toxic and carcinogenic Aflatoxin Metabolism Aflatoxin Action Psoralens Psoralens are a class of photo-mutagenic and photo-chemotherapeutic molecules that covalently modify nucleic acids Iintercalate into and photoalkylate double stranded DNA. Primary targets of psoralens are thymidine residues Form both monoadducts and interstrand crosslinks Reaction takes place between the 3,4 (pyrone) or 4',5' (furan) double bonds of the psoralen and the 5,6 double bond in pyrimidines . Psoralens – DNA cross links Psoralens • Celery contains up to 100ug/100g • Stressed celery can contain 100x that amount • Celery pickers frequently develop skin rashes as an occupational hazard • Interestingly, they are also used to treat a variety of skin diseases Solanines 15 mg per 200g potato Most concentrated in green layer under skin Cholinesterase inhibitors Teratogens (cause birth defects) Amounys increase in diseased potatos > 40 mg/200g considered toxic