1. Genetic Toxicology
Assessment of the effects induced by physical or
chemical agents on both DNA and on the genetic
processes of living cells

2. Health impact of genetic alterations
• Somatic cells
• Germ cells

3. Mechanisms of induction of genetic
alterations
• DNA damage
• DNA repair
• Base excision repair
• Nucleotide excision repair
• Double strand break repair
Homologous recombination
Nonhomologous end-joining
• Mismatch repair

4. Formation of gene mutations
• Somatic cells
• Germ cells

6. Assays for detecting genetic alterations
Goals:
• Identifying hazardous mutagenic chemicals .
• DRC and mutagenic mechanisms
Forward & reverse (backward) mutations:
 Forward mutations are genetic alterations in a
wild-type gene detected by a change in phenotype
due to alteration or loss of gene function.
-Reverse mutation restores gene function in a
mutant (return to wild type phenotype)

7. DNA damage and Repair assays
• Focusing on DNA damage rather than the mutational
consequences
• Either direct (chemical adducts or strand breaks) or
indirect (repair mechanisms)
• COMET assay (DNA release then electrophoresis)
Genetic alterations in nonmammalian
Eukaryotes)
• Gene mutations & chromosome aberration
Sex-linked recessive lethal (SLRL) test (fruit fly
Drosophila)
• Mitotic recombination

8. Gene mutation in mammals
• Gene mutation in vitro
Detection of forward mutation using tissue
culture
• Gene mutation in vivo
Intact animals used for genetic alteration in
certain tissues
• Transgenic assay

9. Mammalian cytogenic assays
• Chromosome aberration
• Micronuclei: membrane bound structures
containing chromosomal fragments
• Sister chromatid exchange detected
cytologically by dof chromatidsifferential
staining
• Aneuploidy: includes:
chromosomsl counting, micronuclei, abnormal
spindles

10. Germ cell mutagenesis
• Gene mutations
• Chromosomal alterations
• Dominant lethal mutations