Methods for screening cellular proliferation using isotope labels

A method of screening an agent for a capacity to induce or inhibit cellular proliferation, said method comprising:

• (a) contacting a cell with the agent;
• (b) contacting the cell with a detectable amount of a stable isotope label which is incorporated into DNA of the cell via de novo nucleotide synthesis pathway;
• and
• (c) detecting the label in the DNA, wherein the amount of label, compared to a control application in which the cell is not exposed to the agent, indicates the extent of cellular proliferation and thereby whether the agent induces or inhibits cellular proliferation.

A method of screening an agent for a capacity to induce or inhibit cellular proliferation in a subject exposed to the agent, said method comprising:

• (a) exposing the subject to the agent;
• (b) administering a detectable amount of a stable isotope label to the subject, wherein the label is incorporated into DNA of the subject via de novo nucleotide synthesis pathway;
• and
• (c) detecting the label in the DNA of a cell of interest in the subject, wherein the amount of label relative to a control application in which the subject is not exposed to the agent indicates the extent of cellular proliferation and thereby whether the agent induces or inhibits cellular proliferation in the subject.

A method for measuring cellular proliferation in a proliferating population of cells, said method comprising:

• (a) contacting the proliferating population of cells with a detectable amount of a first label, wherein the first label comprises a stable isotope label which is incorporated into DNA via de novo nucleotide synthesis pathway;
• (b) detecting the first label incorporated into the DNA to measure cellular proliferation in the proliferating population of cells;
• (c) contacting the proliferating population of cells with a detectable amount of a second label, wherein the second label comprises a radioactive isotope label which is incorporated into DNA via de novo nucleotide synthesis pathway;
• and
• (d) detecting the second label incorporated into the DNA to measure cellular proliferation in the proliferating population of cells.

A method for determining the susceptibility of a subject to a disease which induces a change in a rate of cellular proliferation in the subject, said method comprising:

• (a) exposing the subject to a condition or an agent which can produce the disease;
• (b) administering a detectable amount of a stable isotope label to the subject, which label is incorporated into DNA of the subject via de novo nucleotide synthesis pathway;
• and
• (c) detecting the label in the DNA of the subject, wherein an increase in label in the DNA of the subject, compared to a control application in which the subject is not exposed to the condition or agent, indicates an increase in the rate of cellular proliferation and susceptibility of the subject to the disease.

A method for determining the susceptibility of a subject to a disease which induces a change in a rate of cellular destruction, said method comprising:

• (a) exposing the subject to a condition or an agent which can produce the disease;
• (b) administering a detectable amount of a stable isotope label to the subject, which label is incorporated into DNA of the subject via de novo nucleotide synthesis pathway;
• and
• (c) detecting the label in the DNA of the subject, wherein a loss of label in the DNA of the subject compared to a control application in which the subject is not exposed to the condition or agent indicates an increase in the rate of cellular destruction and susceptibility of the subject to the disease.