Genetic toxicology

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Genetic toxicology

  1. 1. Genetic ToxicologyAssessment of the effects induced by physical orchemical agents on both DNA and on the genetic processes of living cells
  2. 2. Health impact of genetic alterations• Somatic cells• Germ cells
  3. 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. 4. Formation of gene mutations• Somatic cells• Germ cells
  5. 5. Assays for detecting genetic alterations Goals:• Identifying hazardous mutagenic chemicals .• DRC and mutagenic mechanismsForward & 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)
  6. 6. 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
  7. 7. 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
  8. 8. 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
  9. 9. Germ cell mutagenesis• Gene mutations• Chromosomal alterations• Dominant lethal mutations

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