# US 8,541,198 B2 · Method for determination and quantification of radiation or genotoxin exposure

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- Number: US 8,541,198 B2
- Document ID: US8541198B2
- Status: Granted
- Kind: B2
- Application number: 13/023,201
- Filed: 2011-02-08
- Published: 2011-12-22
- Granted: 2013-09-24
- Earliest claimed: 2004-01-30
- Assignees: Dana-Farber Cancer Institute, Inc.
- Applicants: Alan D. D'Andrea
- Inventors: Alan D. D'Andrea
- Web page: https://patentgrep.com/patent/US8541198B2

## CPC

- C07K 14/47: from mammals
- C07K 16/18: against material from animals or humans
- G01N 33/5014: {for testing toxicity}
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention discloses methods for detecting exposure of a living subject to genotoxic agents, testing sensitivity to a genotoxic agent, and determining DNA damage caused by exposure to an agent, comprising detecting the presence of FANCD2-containing foci from a sample collected from said subject. The presence of concentrated foci is indicative of DNA damage, and the degree of foci formation is correlated with degree of exposure. Diagnostic reagents contain a ligand that binds to human FANCD2 associated with a detectable label. Kits for detecting DNA damage in a biological sample contain such diagnostic reagents and signal detection components. The invention further discloses methods for identifying agents which modulate the ability of FANCD2-containing foci to form. Among other things, such agents are potentially useful chemosensitizing agents or may confer protection against damage caused by genotoxic agents.

## Claims

### Claim 1

A method of detecting exposure to a genotoxic agent, comprising:
(a) identifying a subject who is at risk of being exposed to said genotoxic agent;
(b) collecting a sample from said subject;
(c) detecting the number of FANCD2-containing foci in said sample;
(d) detecting the number of FANCD2-containing foci in a control sample; and
(e) comparing the number of FANCD2-containing foci detected in (c) with the number of FANCD2-containing foci detected in (d),
wherein if the number of FANCD2-containing foci detected in (c) exceeds the number of FANCD2-containing foci detected in (d), said exposure to said genotoxic agent is detected.

### Claim 2 (depends on 1)

The method of claim 1, further comprising contacting said sample with a ligand which binds to human FANCD2 of SEQ ID NO: 1, wherein said ligand is associated with a label which provides a detectable signal.

### Claim 3 (depends on 2)

The method of claim 2, wherein said ligand comprises a protein that binds to human FANCD2 of SEQ ID NO: 1 and is fused in frame with a fluorophore.

### Claim 4 (depends on 1)

The method of claim 1, further comprising before step (d), a step of exposing said control sample to said genotoxic agent.