QUESTION 1 1. 2-Nitrobenzanthrone (2-NBA) has recently been detec...

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QUESTION 1 1. 2-Nitrobenzanthrone (2-NBA) has recently been detected in ambient air particulate matter. Its isomer 3-nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust. The only difference between these two compounds is the position of nitro group. Neither compound alone shows DNA adduct formation (data not shown). DNA adduct formation can be measured by incubating xenobiotics with liver microsomes or hepatocytes and measuring the formation of DNA adducts by thin layer chromatography. The presence of radioactive spots indicates the formation of DNA adducts The figure below assesses the effect of 2- NBA and 3-NBA on adduct formation. Which of the following statements are consistent with this data (select all that apply)? A.3-NBA is modified in the liver to a DNA-reactive metabolite B. 2-NBA is modified in the liver to a DNA-reactive metabolite C.3-NBA appears to be a carcinogen D.2-NBA is not a carcinogen E. The structure below is a likely Phase I metabolite of 3-NBA NH2 QUESTION 2 1. Lyme Disease resulting from an infection by the bacterium Borrelia burgdorferi, significantly increases an individual's susceptibility to mercury poisoning. Given what you have learned this week about toxin biotransformations, explain why this is the case (Limit 4-5 sentences) QUESTION 3 1. The compound below is a central nervous system toxicant that also stimulates smooth muscle and can lead to death from cardiac arrhythmia. CH3 N HN N N CH3 Dogs are particularly susceptible to poisoning by this compound, but only extreme doses can lead to serious complications in humans. The chart below shows the oral LD50s for the compound above. LD50 Half-Life Dog 300 mg/kg 17 hr Human 1200 mg/kg 2 hr Given the data, provide a plausible explanation of why the half-life and LD50 are so different for this toxicant (limit 3-4 sentences) The picture below depicts the structure of a parent xenobiotic and its metabolite. Given what you have learned about what Phase I and Phase II biotransformation reactions do to xenobiotics, which structure depicts the metabolite (select one)? H O CI N O O CI N HO H A B A. Chemical A B. Chemical B QUESTION 5 1. The picture below depicts the structure of a xenobiotic and its metabolite Given what you have learned about what Phase I and Phase II biotransformation reactions do to xenobiotics, which structure depicts the metabolite (select one)? H N N CH3 CH3 o O HO A B A. Compound A B. Compound B QUESTION 6 1. The picture below depicts the structure of a xenobiotic and its metabolite. Given what you have learned about what Phase I and Phase II biotransformation reactions do to xenobiotics, which structure depicts the metabolite (select one)? o O CH3 CH3 / / H3C. N N H3C N N 11 // O N N N N H CH3 A B A. Compound A B. Compound B QUESTION 7 The picture below depicts the structure of a xenobiotic and its metabolite. Given what you have learned about what Phase I and Phase II biotransformation reactions do to xenobiotics, which structure depicts the metabolite (select one)? NH2 NH2 O N N N OCH3 HO3SO A B A. Compound A B. Compound B The reaction in the figure below are biotransformations of xenobiotics. Match the reaction with whether it is a Phase I or Phase II biotransformation OH o A HC HO OH OH B HO C N CH3 HCI N H CH3 CH3 CI D O2N S O2N CI H N HO N OH H NH2 C Reaction A A. Phase II Reaction B B. Phase I Reaction C C. Phase I C Reaction D D. Phase II QUESTION 9 1. Which of the following are tissues/organ sites have the potential to mediate Phase I biotransformations of toxins (select all that apply)? A. Intestines B. Liver C. Heart D. Lungs E. Skin 2 points QUESTION 10 1. Which of the following functional groups are commonly conjugated to xenobiotics during Phase II biotransformations (select all that apply)? A. Aldehyde Group B. Acetyl Groups C. Glucuronide D. Glutamate E. Alcohol Group QUESTION 11 1. Which of the statements about Cytochrome P450 biotransfomations of xenobiotics are true (select all that apply)? A. Cytochrome P450 enzymes can be inhibited by eenobioticsCYP450 B. CYP450 enzymes catalyze the glucoronidation of xenobiotics C. Dietary intake can induce the activity of CYP450 enzymes D. The highest tissue levels of CYP450 enzymes is in the small intestines E. Poor biotransformation of a xenobiotic can be due to a mutation in a cytochrome P450 enzyme QUESTION 12 The structures below are of xenobiotics or reactive metabolites of xenobiotics. In the blank provided, give the chemical name of the reactive group (e.g. aldehyde, epoxide). If there is no reactive group, put none. A o CI OH H N B CI NH C F F F D HN N N N E N NH2 6

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