DNA FRAGMENTATION ASSAY

1 . A method of identifying an agent that modifies the formation of DNA fragments, the method comprising:

a) providing cells in an array of receptacles;

b) adding an agent to at least one receptacle;

c) incubating the agent with the cells for a predetermined period of time;

d) lysing the cells;

e) adding a detectable compound capable of intercalating into DNA fragments to said at least one receptacle;

f) measuring the amount of detectable compound intercalated; and

g) comparing the amount of intercalated detectable compound to a control to determine a difference

thereby identifying said agent as a modifying agent when the difference exceeds a predetermined threshold.

2 . A method of identifying an agent that modifies the formation of DNA fragments, the method comprising:

a) providing cells in an array of receptacles;

b) adding to at least one receptacle a component selected from the group consisting of an inducer, an inhibitor, a modulator, a modulator of the inducer and a modulator of the inhibitor;

c) incubating the component with the cells for a predetermined period of time;

d) adding an agent to said at least one receptacle;

e) incubating the agent with the cells for a predetermined period of time;

f) lysing the cells;

g) adding a detectable compound capable of intercalating into DNA fragments to said at least one receptacle;

h) measuring the amount of detectable compound intercalated; and

i) comparing the amount of intercalated detectable compound to a control to determine a difference

thereby identifying said agent as a modifying agent when the difference exceeds a predetermined threshold.

3 . The method of claim 2 wherein step (d) is combined with step (b) and step (e) is combined with step (c).

4 . The method of claim 1 or 2 wherein chromosomal DNA is separated from DNA fragments before measuring the amount of detectable compound intercalated.

5 . The method of claim 4 wherein the chromosomal DNA is separated from the double-stranded DNA fragments by a process selected from the group consisting of centrifugation, filtration, sedimentation, electrophoresis, size-exclusion, precipitation and affinity purification.

6 . The method of claim 1 or 2 wherein the detectable compound comprises a substance selected from the group consisting of a radioactive isotope, a chemical that fluoresces, a peptide tag, a scintillant-activating compound, an enzyme and an epitope recognized by a detectable antibody.

7 . The method of claim 6 wherein the detectable compound comprises a substance selected from the group consisting of PicoGreen, SYBR Green, TOTO, YOPRO, BENA435, Hoechst 33258, Hoechst 33342, DAPI, DRAQ5, OliGreen and propidium iodide.

8 . The method of claim 1 or 2 wherein the cell comprises a prokaryotic cell.

9 . The method of claim 1 or 2 wherein the cell comprises a eukaryotic cell.

10 . The method of claim 1 or 2 wherein the cell is transiently or stably transformed to overexpress at least one protein.

11 . The method of claim 1 or 2 wherein the cell is provided following isolation from a biological sample.

12 . The method of claim 11 wherein the biological sample is from a human.

13 . The method of claim 1 or 2 wherein the cell is an HL60 cell.

14 . The method of claim 1 or 2 wherein one or more steps are performed by a robotic device.

15 . The method of claim 1 or 2 wherein the cells are lysed by a process selected from the group consisting of a lysis buffer containing a detergent, a hypotonic lysis buffer, sonication and freeze/thaw.

16 . The method of claim 1 wherein RNAse is added during step (d) or step (e).

17 . The method of claim 2 wherein RNAse is added during step (f) or step (g).

18 . A method of identifying an agent that modifies the formation of DNA fragments, the method comprising

a) providing cells in an array of receptacles;

b) adding an agent to at least one receptacle;

c) incubating the agent with the cells for a predetermined period of time;

d) adding a detectable compound capable of intercalating into DNA fragments to said at least one receptacle;

e) measuring the amount of detectable compound intercalated; and

f) comparing the amount of intercalated detectable compound to a control to determine a difference

thereby identifying said agent as a modifying agent when the difference exceeds a predetermined threshold.

19 . A method of identifying an agent that modifies the formation of DNA fragments, the method comprising:

a) providing cells in an array of receptacles;

b) adding to at least one receptacle a component selected from the group consisting of an inducer, an inhibitor, a modulator, a modulator of the inducer and a modulator of the inhibitor;

c) incubating the component with the cells for a predetermined period of time;

d) adding an agent to said at least one receptacle;

e) incubating the agent with the cells for a predetermined period of time;

f) adding a detectable compound capable of intercalating into DNA fragments to said at least one receptacle;

g) measuring the amount of detectable compound intercalated; and

h) comparing the amount of intercalated detectable compound to a control to determine a difference

thereby identifying said agent as a modifying agent when the difference exceeds a predetermined threshold.

20 . The method of claim 1 further comprising providing a second array of receptacles wherein step (d) further comprises separating supernatant from cell debris and step (e) further comprises adding a detectable compound capable of intercalating into DNA fragments to at least one receptacle of said second array of receptacles containing a sample of said separated supernatant.

21 . The method of claim 2 further comprising providing a second array of receptacles wherein step (f) further comprises separating supernatant from cell debris and step (g) further comprises adding a detectable compound capable of intercalating into DNA fragments to at least one receptacle of said second array of receptacles containing a sample of said separated supernatant.

22 . An assay system for identifying an agent that modifies the formation of DNA fragments, the assay system comprising:

a) an array of receptacles;

b) a lysis buffer;

c) a detectable compound capable of intercalating into DNA; and

d) at least one component wherein the component is selected from the group consisting of the agent(s), an inducer(s), an inhibitor, a modulator(s), a modulator(s) of the inducer(s), a modulator(s) of the inhibitor(s), control(s) and cells.

23 . A kit comprising at least one element of the assay system of claim 20 - 22 and instructions for use.

24 . A method of diagnosing or monitoring a treatment of a disease wherein a biomarker for the disease comprises the formation of DNA fragments, the method comprising:

a) providing a biological sample in an array of receptacles;

b) adding a detectable compound capable of intercalating into DNA fragments to at least one receptacle;

c) measuring the amount of detectable compound intercalated; and

d) comparing the amount of intercalated detectable compound to a reference to determine a difference

thereby diagnosing or monitoring the treatment of the disease when the difference exceeds a predetermined threshold.

25 . The method of claim 24 wherein the biological sample comprises a sample selected from the group consisting of cells, tissues, organs, and blood.

26 . An assay system for diagnosing or monitoring a treatment of a disease wherein a biomarker for the disease comprises the formation of DNA fragments, the assay system comprising:

a) an array of receptacles;

b) a detectable compound capable of intercalating into DNA; and

d) at least one control.