Munariy lecture 3

Question 1

Definition biomarker

Answer 1

• measurable indicator of some biological state or condition that links a specific environmental exposure to a health outcome
• play an important role in understanding the relationships between exposure to environmental chemicals and the development of adverse effects at individual and population levels

Question 2

2 classes of biomarkers?

Answer 2

• Biomarkers of exposure
• Biomarkers of effect

Question 3

Biomarkers of exposure

Answer 3

• Give significant information about the interaction of pollutants with organisms, at different levels of biological organization (from molecules to organism)
• but do not provide information about the toxicological effects on organisms

Question 4

Biomarkers of effects

Answer 4

-Provide information on both exposure and effects of pollutants on organisms

Question 5

Biomarkers exposure vs biomarkers effects

Answer 5

Question 6

What are specific biomarkers?

Answer 6

• Biological responses that occur in an organism after exposure to a specific category of contaminants
• Example: imposex (development of male sex organs on female organisms)

Question 7

What are generic biomarkers?

Answer 7

• molecular, cellular, biochemical, physiological and behavioural responses of the organism that are caused not by a single category of compounds but by different classes of substances
• Example: DNA damage, alterations of
  the immune system etc…

Question 8

Biotransformation enzymes (example of biomarker)

Answer 8

• Foreign chemicals (xenobiotics) are lipophilic so poorly excretable
• They still undergo metabolic conversion in a process called biotransformation
• Biotransformation, mediated by enzymes, results in conversion of parent chemical to more polar and excretable metabolites
• The activity of these enzymes may be induced or inhibited upon exposure to xenobiotics

Question 9

What is the goal of biotransformation?

Answer 9

• To facilitate the removal of toxic chemicals from an animal, which, unless excreted, could accumulate to harmful levels

Question 10

What are the 2 major types of enzymes involved in xenobiotic biotransformation? And where are they present?

Answer 10

• Phase I enzymes and Phase II enzymes
• Present in the liver or similar tissues
  Phase I enzymes: in ER
  Phase II enzymes: in cytosol

Question 11

Phase I enzymes

Answer 11

• introduce or expose functional groups (-OH, -NH2, -SH) on the drug with the goal of increasing the polarity of the compound
• grouped into three categories: oxidation, reduction, and hydrolysis
• converts these hydrophobic, lipophilic compounds into more water soluble compounds that can be excreted
• Oxidation most common phase
• Hepatic cytochrome P450 system is the most important of the phase I oxidation systems
• Metabolites produced are inactive but, in some instances, active metabolites are also formed

Question 12

Phase II enzymes

Answer 12

• involve a conjugation of the xenobiotic parent compound or its metabolites with an endogenous ligand
• catalyze these synthetic conjugation reactions, thus facilitating the excretion of chemicals by the addition of more polar groups
• Glutathione S-transferase (GST) catalyzes the conjugation of glutathione with xenobiotic compounds

Question 13

What are conjugations? (Phase 2 enzymes)

Answer 13

Addition reactions in which large and often polar chemical groups or compounds such as sugars and amino acids are covalently added to xenobiotic chemical compounds and drugs