# US 5,346,814 A · Method of detecting cell response to cell-damaging energy

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- Number: US 5,346,814 A
- Document ID: US5346814A
- Status: Granted
- Kind: A
- Application number: 07/961,268
- Filed: 1992-10-14
- Granted: 1994-09-13
- Earliest claimed: 1992-10-14
- Assignees: The Board of Trustees of the Leland Stanford Jr. University
- Inventors: George M. Hahn; Alie H. Saad; Amato J. Giaccia
- Web page: https://patentgrep.com/patent/US5346814A

## CPC

- G01N 33/5011: {for testing antineoplastic activity}
- A61K 49/0004: {Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions}
- G01N 33/5005: {involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025)}
- Y10S 435/968: High energy substrates, e.g. fluorescent, chemiluminescent, radioactive
- 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)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

A method of assessing a cell's susceptibility to cell-damaging energy, such as ionizing radiation and heat, is disclosed. The method is based on measurable changes in voltage-dependent potassium channel currents in the cell in response to the energy. Also disclosed is a method for screening drugs which are effective to sensitize a cell to cell-damaging radiation.

## Claims

### Claim 1

A method of assessing the susceptibility of a cell of a known origin to cell-damaging energy, comprising
exposing a cell from a known origin to an amount of cell-damaging energy effective to increase a potassium channel current in said cell,
measuring a voltage-dependent potassium current in a cell from the known origin, before and after said exposing, and
using the change in the measured current before and after exposing, to assess the ability of a cell from the known origin to resist said energy.

### Claim 2 (depends on 1)

The method of claim 1, wherein said cell-damaging energy is ionizing radiation.

### Claim 3 (depends on 2)

The method of claim 2, wherein said cell damaging energy is x-irradiation.

### Claim 4 (depends on 2)

The method of claim 2, wherein said exposing includes contacting the cells with a high-energy radiation emitter.

### Claim 5 (depends on 1)

The method of claim 1, wherein said cell-damaging energy is heat.

### Claim 6 (depends on 5)

The method of claim 5, wherein said heating is carried out by microwave irradiation.

### Claim 7 (depends on 5)

The method of claim 5, wherein said heating is carried out by elevating the temperature of the cell, in vitro.

### Claim 8 (depends on 1)

The method of claim 1, for use in optimizing treatment conditions for treating cancer cells in a human patient, wherein the origin of the cell being assessed is a population of cancer cells from the patient's body, and said measuring step is carried out on said cell in vitro.

### Claim 9 (depends on 8)

The method of claim 8, wherein said exposing and measuring steps are carried out on the cell of known origin cultured in vitro.

### Claim 10 (depends on 8)

The method of claim 8, wherein said exposing includes exposing a portion of the patient, and said measuring includes measuring the potassium currents of cells obtained from the exposed portion of the body before and after said exposing.

### Claim 11

A method for screening compounds which are effective to sensitize tumor cells to cell-damaging energy, comprising
incubating a test compound with a cultured cell that exhibits an inducible voltage-dependent potassium current upon exposure to cell-damaging energy,
during said incubating, exposing the cell to an amount of the cell-damaging energy effective to increase a potassium channel current in said cell,
measuring the voltage-dependent potassium current in the cell before and after said incubating, and
using the change in voltage-dependent potassium current measured before and after said incubating as an indicator of the test compound's ability to block induction of increased potassium currents in response to exposure to cell-damaging energy.

### Claim 12 (depends on 11)

The method of claim 11, wherein the potassium current is measured by whole cell voltage-clamping.

### Claim 13 (depends on 11)

The method of claim 11, wherein said cell-damaging energy is ionizing radiation.

### Claim 14 (depends on 13)

The method of claim 13, wherein the cell is exposed to between 10 and 1500 cGy of .sup.137 Cs .gamma.-radiation.

### Claim 15 (depends on 13)

The method of claim 13, wherein the cell is an A549 cell.

### Claim 16 (depends on 11)

The method of claim 11, wherein said cell-damaging energy is heat.

### Claim 17 (depends on 16)

The method of claim 16, wherein the cell is exposed to a temperature of about 45 degrees C, for a period of between 1 and 45 minutes.