Mutagenesis and genetic toxicology

Mechanisms of mutagenesis and genetic toxicology of agents.

1. MUTAGENESIS AND GENETIC
TOXICOLOGY.
BY DAVID ENOMA

2. BASIC GENETICS
Deoxyribonucleic acid (DNA) is the fundamental
structure that contains all of the information required
for cellular function.

3. CENTRAL DOGMA
The DNA is transcribed into RNA (ribonucleic acid)
where uracil is used instead of thymine. This serves as
the template upon which a series of amino acids are
assembled to make a protein.
The sequence of amino acids is determined by the
order of the nucleotide bases that are decoded in
groups of three bases called codons

5. Mutation is both the process by which a gene (or
chromosome) changes structurally and the end result of
that process.
Several types of mutations are known:
Substitution
Deletion
Insertion
Frameshift(Berg, Tymoczko, & Stryer, 2002).
Misenseand Nonsense mutations
MUTATION

8. CHROMOSOMAL ABERATIONS

9. CHROMOSOMAL ABERATIONS

10. PHENOTYPIC EXPRESSIONS OF MUTATIONS

11. MUTAGENESIS
Mutagenesis is the process of generating a genetic
mutation. This may occur spontaneously or be
induced by mutagens. (Mutagenesis, 2006).
This change or alteration can subsequently be
inherited from one cell to the next or not.
They can be in the form of point mutation, a deletion,
or a duplication in the DNA sequence.

12. MECHANISM OF GENOTOXICMUTAGENESIS

13. MUTAGENS
Mutagens are substances that change the genetic information of
an organism, usually by changing DNA.
Types of mutagens:
Chemical
Alkylating agents
Base analog
Methylatingagents
DNA intercalating agent
Reactive oxygen species
UV radiation
Ionizing radiation

14. GENETIC TOXICOLOGY
Genetic toxicology gained recognition as a discipline in
1969 when Dr.Alexander Hollaenderand other
geneticists founded the Environmental Mutagen Society.
(Brusick, 2013).
Genetic toxicology is the study of the damage to
deoxyribonucleic acid (DNA).
Genetic toxicology, as a subspecialty of toxicology, identifies
and analyzesthe action of agents with toxicity directed toward
the hereditary components of living systems. (Brusick, 2013).

15. GENETIC TOXICANTS
Genotoxicantsare characterized by several properties
including,
Altering the nucleotide sequence of genes,
Altering the chromosomal structure (Clastogenicity),
Altering chromosomal number (Aneuploidy),
Affecting expression of genes (Epigeneticity) (Hayes &
Kruger, 2014).

16. APPLICATIONS OF GENETIC TOXICOLOGY
In vivo genetic toxicology tests measure direct DNA
damage or the formation of gene or chromosomal
mutations, and are used to predict the mutagenic and
carcinogenic potential of compounds for regulatory
purposes and/or to follow-up positive results from in
vitro testing.

17. AMES ASSAY
The Bacterial Reverse Mutation Assay, also known as
the Ames Assay
The technique uses many different bacterial strains in
order to compare the different changes in the genetic
material.
The types of mutations detected are frame shifts and
base substitutions

18. IN VITRO TESTING
The purpose of in vitro testing is to determine
whether a substrate, product, or environmental
factor induces genetic damage.
The types of aberrations detected in cells
affected by a genotoxicsubstance are
chromatid and chromosome gaps, aberrations
etc.

19. IN VIVO TESTING
The purpose for in vivo testing is to determine the
potential of DNA damage that can affect
chromosomal structure or disturb the mitotic
apparatus that changes chromosome number.
It can also detect genotoxicagents missed inin
vitrotests.

20. COMET ASSAY
Comet assays are one of the most common tests for
genotoxicity.
The technique involves lysing cells using detergents and
salts.
The DNA released from the lysed cell is electrophoresed
in an agarosegel under neutral pH conditions.
Cells containing DNA with an increased number of
double-strand breaks will migrate more quickly to the
anode.

21. REFERENCES
https://www.nature.com/subjects/mutagenesis
Berg, J. M., Tymoczko, J. L., & Stryer, L. (2002). Biochemistry,
Fifth Edition: W.H. Freeman.
Brusick, D. (2013). Principles of Genetic Toxicology: Springer
US.
US National Library of Medicine: https://ghr.nlm.nih.gov
James M. Parry and Elizabeth M. Parry (eds.), Genetic
Toxicology: Principles and Methods, Methods in Molecular
Biology, vol. 817, Springer Science+BusinessMedia, LLC 2012