Mutagens and their actions

1. Mutagensand their actions
Mutagens and Chan Ho Yin, Aurora (02690763)
Chen Yiwei, Echo (01790443)
Co NgaiNa, Chloe (02715283)
Lam Kit Ming,Germaine(02770293)

2. „Mutation
„Spontaneous Mutation & Induced Mutation
„Mutagen
„ChemicalMutagens
„Radiation
„BiologicalMutagens
„Conclusion
Introduction

3. „The process that produces an inheritable alteration in
„DNA Structure
„Chromosome Structure
„There are two types of mutations
„Spontaneous Mutation
„Induced Mutation
Mutation

4. „ Spontaneous Mutation
„Natural error during DNA replication or recombination
„Caused by background radiation
„Arise randomly as a result in cells
„NO ARTIFICIAL TREATMENT
Spontaneous Mutation vs.
Induced Mutation

5. Spontaneous Mutation vs.
Induced Mutation
„ Induced Mutation
„Caused by exposure to known mutagenic agents
--Mutagens

6. Mutagen
„A natural or human-made agent which can alter the structure or sequence of genetic material and induce
Mutation

7. „There are three main types ofmutagensclassifying by their sources
„ChemicalMutagens
„Radiation
„BiologicalMutagens

8. •
Transposable element
•
Ionizing Radiation
•
UV Radiation
•
Base analogs
•
Chemical modification agents
•
Intercalating agents
BiologicalMutagens
Radiation
ChemicalMutagens

9. „Chemicals structurally resemble normal bases, purinesand pyrimidines
„Incorporate into DNA during replication
„Lead to incorrect insertion of nucleotides opposite them in replication
ChemicalMutagens-Base analogs

10. „5-Bromouracil(5-BU)
„2-Aminopurine(2-AP)
For Example

11. „resemblesThymine(T)
„has Br atom at C-5 instead of methyl group as in T
„can incorporate into DNA and pair with either A or G due to tautomerization
5-Bromouracil
analog of a pyrimidine

12. * TAUTOMERIZATION –spontaneous structural alternations between 2 forms, ketoform and enolform
5-Bromouracil
analog of a pyrimidine

13. Mechanism of 5-
Bromouracil

14. Mechanism of 5-
Bromouracil

16. „Chemicals which alter structure and pairing properties of normal bases
„Active on both replicating and non- replicating DNA
„Result in mutation upon DNA replication by forming baseless sites or mispair
„Two common chemical modification agents
„Alkylatingagents
„Deaminatingagents
ChemicalMutagens- Chemical Mutagens-
Chemical modification agents

17. „Modify the normal bases by adding alkyl groups
„Common alkylatingagents
„Ethylmethanesulfonate(EMS)
„Nitrosoguanidine(NG)
„Di-(2-chloroethyl) sulfide (Sulfur mustard)
„Di-(2-chloroethyl) methylamine (Nitrogen mustard)
Alkylatingagents Alkylating agents

18. Ethylmethanesulfonate(EMS)
Alkylatingagents Alkylating agents

19. Ethylatebase’s 7-N & 6-O positions
Mechanism of
Ethylmethanesulfonate(EMS)
Ethylmethane sulfonate (

20. Ethylatebase’s 7-N & 6-O positions
Mechanism of
Ethylmethanesulfonate(EMS)
Ethylmethane sulfonate (

21. „Oxidative deaminationof amino group in Adenine (A), Guanine (G) and Cytosine (C)
Deaminatingagents Deaminating agents

22. „Nitrous acid (HNO2) is one of common deaminatingagents
„Convert the amino group (-NH2) into ketogroup (=O)
„Change H-bonding potential of the modified bases
Deaminatingagents Deaminating agents

23. Adenine (A) →Hydroxanthine
Mechanism of Nitrous acid

24. Cytosine (C) →Urail
Mechanism of Nitrous acid

25. Guanine (G) →Xanthine
Mechanism of Nitrous acid

26. „A group of aromatic organic molecules
„Roughly the same dimensions as a nitrogenous base pair
„Intercalate or wedge between the base pair
ChemicalMutagens- Intercalating agents
Chemical Mutagens-

27. „Cause addition or deletion of base pairs of intact DNA
„Alter reading frame of gene
„Result in non-functional gene product
ChemicalMutagens- Intercalating agents
Chemical Mutagens-

28. Mechanism of
Intercalating agents

29. Mechanism of
Intercalating agents
„Common intercalating agents
„2,8-Diamino acridine(proflavin)
„Acridineorange

30. „Ionisingradiation
e.g. x rays, γrays, cosmic rays
„Non-ionisingradiation
e.g. UV radiation
PhysicalMutagens Physical Mutagens

31. „Natural Sources:
Sunlight, outer space
„Artificial Sources:
Medical diagnostic, powerplant
Ionizing Radiation
(high energy and penetrating)

32. „Mechanism
„Production of highly reactive free radicals (OH•radicals)
„Interaction between the radicals and DNA, proteins, lipids in cell membrane etc.
Ionizing Radiation
(high energy and penetrating)

33. „Effects
„Organelle failure
„Cell division blockage
„Cell death
Ionizing Radiation
(high energy and penetrating)

34. „Breaks in one or both strands
(can lead to rearrangements, deletions, chromosome loss Ædeath if unrepaired)
„Damage to/loss of bases (mutation)
„Crosslinkingof DNA to itself or proteins
Interaction with DNA

35. Interaction with DNA
CATCACCTGTACCAGTAGTGGACATGGTdeletionCATTCACCTGTACCAGTAAGTGGACATGGTnormal sequence
Base pair mutation

36. Take UV radiationas an example
„Its wavelengths are preferentially absorbed by bases of DNA and by aromatic amino acids of proteins
„Normally classified in terms of its wavelengths:
UV-A, UV-B, UV-C (in decreasing order of wavelengths)
Non-Ionizing Radiation
(Less energy, Non-penetrating)

37. Non-Ionizing Radiation
(Less energy, Non-penetrating)
„Mechanism
„Formation ofThymine dimers
„These dimerscause the strand to buckle, disrupting normal base pairing
„Prevent normal replication and transcription

38. Formation ofThymine-thymine dimer

40. „Transposable element
„Insertions result in dysfunction of genes
„Common biologicalmutagens
„Rubella virus
„Cytomegalovirus
„Hepatitis B virus
BiologicalMutagens Biological Mutagens

41. Biological agents
BiologicalMutagens Biological Mutagens

42. Conclusion
„Mutation
„Spontaneous Mutation & Induced Mutation
„Mutagen
„ChemicalMutagens
„Radiation
„BiologicalMutagens
„Exposure tomutagenmay induce mutation!

43. References
„Principles of Genetics
„An Introduction of Genetic Analysis
„DNA replication
„http://pharmacology.unmc.edu/cancer/antibio.htm

44. Thank You
Chan Ho Yin, Aurora (02690763)
Chen Yiwei, Echo (01790443)
Co NgaiNa, Chloe (02715283)
Lam Kit Ming,Germaine(02770293)