Its about gene and DNA damage on nanomaterials

1. ARAVINTH
MSc-Nanoscience and Technology
Alagappa University
Karaikudi

2. INTRODUCTION
 Mutation is a broad term covering a whole range of
changes to the informational molecule, DNA (made up
of the four nucleotides: the purines, adenine and
guanine, and the pyrimidines, thymine and cytosine)
packaged into chromosomes, of an organism from gene
changes to modifications of the number and structure
of chromosomes
 Point mutations are changes to the sequence of
nucleotides and may involve the substitution of
individual bases

3. GENOTOXICITY
 Genotoxicity describes the property of chemical
agents that damages the genetic information
within a cell causing mutations, which may lead to
cancer
 The alteration can have direct or indirect effects
on the DNA: the induction of mutations and direct
DNA damage leading to mutations

4. THESTUDYOFCHEMICAL,PHYSICALORBIOLOGICALAGENTS THATCAN
CHANGETHESEQUENCEORSTRUCTUREOFDNA
What is Genetic Toxicology
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 DNA damage can be:
 at nucleotide level in DNA, or at
the chromosomal level
 induced by direct mechanisms (chemical or
metabolite interacts with DNA)
 induced by indirect mechanisms (chemical
or metabolite affects other cellular
macromolecules, e.g. mitotic spindle fibers)

5. WHY WE EVALUATE GENOTOXICITY
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Germ Cells
spermatocytes, oocytes Somatic Cells
Heritable Damage
(genetic damage to
offspring)
Infertility Cancer Other Diseases
DNA damage is associated with many human diseases

6. MECHANISM
 The genotoxic substances induce damage to the
genetic material in the cells through interactions
with the DNA sequence and structure
 For example, the transition metal chromium
interacts with DNA in its high-valent oxidation state
so to incur DNA lesions leading to carcinogenesis
 The metastable oxidation state Cr(V) is achieved
through reductive activation

7.  Another example of a genotoxic substance causing
DNA damage are pyrrolizidine alkaloids (PAs)
 These substances are found mainly in plant species
and are poisonous to animals, including humans;
about half of them have been identified as
genotoxic and many as tumorigenic

8.  Hazard identification/Lead prioritization
 Companies want products to be safe and to be seen as safe for
intended uses
 Predict whether a chemical is a carcinogen
 Predict whether a chemical could cause heritable germ cell
damage
 Early testing “screening” allows Companies/Regulators to
prioritize chemicals to spend
further resources on (e.g. EPA ToxCast™)
 Mechanistic information
 Determine mechanism of action for carcinogens (genotoxic vs.
non-genotoxic)
 Basic science: study of DNA damage/repair
OBJECTIVES OF GENETIC TOXICOLOGY
TESTING
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9. WHAT ARE THE GENETIC TOXICOLOGY TOOLS
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 Hundreds of assays developed to measure DNA damage
 Assays grouped by endpoint measured
Types of DNA damage endpoints include:
 Mutations
 Changes in chromosome structure or number
 DNA damage
 DNA repair
 Biomarkers of DNA damage
Endpoints can be measured in:
 bacteria, yeast, fungi, plants, invertebrates, mammalian cells in
culture, animals and humans