International E co G en Incorporated

Photo Copyright by Michael Easton



Types of Genetic Damage

 

Genotoxic damage may be divided into 3 levels of intensity as determined by their sensitivity to detection by flow cytometry. The level of damage can increase with both increasing mutagen concentration and increasing exposure time at the same concentration.

 

Level 1

Mutation Type

  • point mutations
  • frame shift mutations

Because there is no net loss or gain of DNA in the sister chromatids and thus the subsequent daughter cells would each have an identical amount of DNA, these mutations are not detectable by flow cytometry. Only molecular genetic methods utilizing gene sequencing analysis can detect these events.

 

Level 2

Mutation Type

  • chromosome or chromatid breaks
    • duplications
    • deletions
    • translocations
    • loss or gain of chromosome fragments
     
  • aneuploidy
    • loss or gain of whole chromosomes

These DNA breakage events that occur in the cell directly affected by the mutagens are detectable by the Comet assay. The observed damage may still be repaired before the cell divides. After cell division any unrepaired damage becomes fixed and is passed on to future generations of cells thus bio-magnifying the prior mutagenic event. This expressed mutagenic damage is readily detectable by flow cytometry for cells in the G0/G1 phase. 

 

Level 3

Mutation Type

  • spindle disruption at metaphase and anaphase
    • attached fragments
    • anaphase bridge
  • dicentric chromosome formation

This type of mutagenic damage prevents normal cell division and is usually cell lethal. The cytotoxic consequences thus prevent the passing on of the mutagenic damage to future generations of cells and prevents bio-magnification of the event. Thus, in nucleated red blood cells (as found in most vertebrates except mammals) for example, this type of damage in the red blood precursor cells would not be detectable in the peripheral blood by flow cytometry. The damage would be detectable by chromosome aberration analysis of the blood precursor cells or by possibly forcing lymphocytes to attempt to divide and then stopping the cell division process at metaphase.



Types of Mutation
Consequences of Mutation
Our DNA Damage Detection Method

BACK I HOME

Updated by Michael Easton 2009.