7 Questions
Why might Joe Schmoe not get lung cancer despite smoking three packs of cigarettes a day?
High activity of DNA repair genes
What is a known outcome of DNA damage?
Cancer
What is the result of Kultima's (2000) study on Valproic Acid?
Increased expression of metallothionein
What is the mechanism of teratogenicity of Valproic Acid?
Unknown
How might Toxicogenomics and DNA microarrays be of value with respect to variability in liver enzymes and DNA repair?
To determine which individuals would be at risk for long-term adverse effects following exposure to certain toxins
Why is Valproic Acid avoided in pregnancy?
Due to its potential to cause birth defects
What is the role of metallothionein in fetal development?
A key cofactor in fetal development
Study Notes
DNA Repair Genes
- DNA repair genes are polymorphic, meaning they function at different levels in different individuals.
- Individuals have varying abilities to repair DNA damaged by toxins, UV radiation, chemotherapy, etc.
DNA Damage and Cancer
- A known outcome of DNA damage is cancer.
- High activity of genes that detoxify carcinogens, low activity of genes that form carcinogenic metabolites, and high activity of DNA repair genes can contribute to an individual's resistance to cancer.
Toxicogenomics and DNA Microarrays
- Toxicogenomics and DNA microarrays can be used to determine which individuals are at risk for long-term adverse effects following toxin exposure.
- They can help identify variability in liver enzymes and DNA repair.
Mechanism of Drug Teratogenicity: Valproic Acid
- Valproic acid is avoided during pregnancy due to birth defects, but the mechanism of teratogenicity is unknown.
- Kultima's (2000) study used toxicogenomics and DNA microarrays to show that valproic acid exposure increases the expression of certain mouse fetal genes.
- One of these genes is metallothionein, which is associated with fetal zinc deficiency, a key cofactor.
Learn how DNA repair genes function differently in individuals, affecting their ability to repair DNA damage from toxins and carcinogens, and the impact on cancer development.
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