A.) You are working in the lab with two known carcinogens found in cigarette smoke: Benzo(a)pyren (BaP) and nitrosamine ketone (NNK). BaP is an aromatic hydrocarbon and the mechanism of carcinogenesis is through oxidation reactions with DNA. NNK is a nitrosoamine.
a. Describe how these two kinds of carcinogens lead to mutations.
b. You mix these two carcinogens with strains of bacteria in the lab in order to induce mutations. However, neither causes any increase in the “background rate” of mutations that you observe in the “negative control” bacteria, leading you to believe that you must have forgotten something or did something wrong. What was the thing you likely forgot?
B.) One way to think about the genome is that it is an elaborate set of instructions for building proteins and regulating their activity. List three steps of gene expression and how they are regulated
a) Benzo[a]pyrene (BaP) is first oxidized inlung cells by enzyme cytochrome P450 oxidase to form benzo[a]pyrene-7,8-epoxide. This compound is metabolized by enzyme epoxide hydrolase, and produce benzo[a]pyrene-7,8-dihydrodiol.After this carcinogen is formed by the action of cytochrome P450 oxidase and convert into benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide. This epoxide binds to to Guanine of DNA covalently, consequently DNA distorts.Due to distortion, replication of DNA disrupts and mutation take place.
Cytochrome P450 oxidase activate the NNK to reactive metabolites that induce the methylation, pyridyloxobutylation and pyridylhydroxybutylation of bases in DNA and form DNA adducts.
b) After mixing these two carcinogens with starins of bacteria you weer not observed any increase in background mutation rate, perhaps your strains were resistant against these carcinogens.
A.) You are working in the lab with two known carcinogens found in cigarette smoke: Benzo(a)pyren...