Isolation of epithelial cells or their biochemical contents from excreta after in vivo isotopic labeling

A method for evaluating a toxic effect on the epithelial tissue of a subject, said method comprising:

• a) exposing said subject to one or more compounds;
• said subject having one or more body spaces wherein said body sapces are in communication with the external environment of said subject;
• b) administering an isotope-labeled substrate to said subject for a period of time sufficient for said isotope-labeled substrate to enter into one or more metabolic pathways of interest and thereby enter into and label one or more targeted molecules of interest within said one or more metabolic pathways of interest in said subject wherein said one or more metabolic pathways of interest are related to at least one biomarker of epithelial tissue toxicity;
• c) obtaining one or more samples from said subject, wherein said one or more samples comprise one or more isotope-labeled targeted molecules of interest and are obtained from said one or more body spaces in communication with the external environment;
• d) measuring the content, rate of incorporation and/or pattern or rate of change in content and/or pattern of isotope labeling of said targeted molecule or molecules of interest;
• e) calculating molecular flux rates in said one or more metabolic pathways of interest based on the content and/or pattern or rate of change of content and/or pattern of isotopic labeling in said molecule or molecules of interest;
• f) measuring the molecular flux rates in said one or more metabolic pathways of interest according to steps b) through e) in a control subject not administered said one or more compounds;
• and
• g) comparing said molecular flux rates in said one or more metabolic pathways of interest in said control subject administered said one or more compounds to said molecular flux rates in said one or more metabolic pathways in said subject not administered said one or more compounds to detect any toxic effect to said exposed subject's epithelial tissue.

A method comprising:

• a) measuring a molecular flux rate of an epithelial tissue biomarker of interest using an isotope;
• b) comparing the results of step a) with a molecular flux rate of an epithelial biomarker of interest in the presence of a compound of interest;
• and
• c) if said compound of interest changes a molecular flux rate of interest, developing said compound as a drug.

A method for detecting the presence or absence of an epithelial disease or monitoring an epithelial disease of a subject, said method comprising:

• a) administering an isotope-labeled substrate to said subject for a period of time sufficient for said isotope-labeled substrate to label at least one targeted molecule of interest in one or more metabolic pathways of interest in one or more cells of epithelial origin in said subject wherein said subject has one or more body spaces wherein said body spaces are in communication with the external environment of said subject;
• b) obtaining one or more samples from said one or more body spaces in said subject, wherein said one or more samples comprise at least one isotope-labeled targeted molecule of interest;
• c) measuring the content, rate of incorporation and/or pattern or rate of change in content and/or pattern of isotope labeling of said at least one targeted molecule of interest;
• d) calculating molecular flux rates in said one or more metabolic pathways of interest based on the content and/or pattern or rate of change of content and/or pattern of isotopic labeling in said at least one targeted molecule of interest;
• and
• e) measuring the molecular flux rates in said one or more metabolic pathways of interest to detect the presence or absence of said epithelial disease or to monitor said epithelial disease in said subject.

A method for detecting the presence or absence of cancerous or pre-cancerous breast cancer or monitoring a treatment of breast cancer in a patient, said method comprising:

• a) administering deuterated water to said patient for a period of time sufficient for said deuterated water to label DNA in one or more breast epithelial cells in said patient;
• b) collecting a sample of said breast epithelial cells comprising said labeled DNA;
• c) measuring the content, rate of incorporation and/or pattern or rate of change in content and/or pattern of isotope labeling of said DNA in said breast epithelial cells;
• and
• d) comparing said rate or pattern to historical data, data obtained from a control subject, data obtained from non-cancerous tissue in the same subject, data obtained from the same subject prior to treatment or, or data obtained from the same subject prior to cancer onset in order to evaluate whether or not there is an increase or decrease in breast epithelial cell proliferation with respect to normal subjects or tissues, to detect the presence or absence of cancerous or pre-cancerous breast cancer, or monitor a treatment of breast cancer in said patient.

A method for detecting the presence or absence of prostate cancer or monitoring a treatment of prostate cancer in a patient, said method comprising:

• a) administering deuterated water to said patient for a period of time sufficient for said deuterated water to label DNA in one or more prostate epithelial cells in said patient;
• b) collecting a sample of said prostate epithelial cells comprising said labeled DNA;
• c) measuring the content, rate of incorporation and/or pattern or rate of change in content and/or pattern of isotope labeling of said DNA in said prostate epithelial cells;
• and
• d) comparing said rate or pattern to historical data, data obtained from a control subject, data obtained from tissue in the same subject, data obtained from the same subject prior to treatment, or data obtained from the same subject prior to cancer onset in order to evaluate whether or not there is an increase or decrease in prostate epithelial cell proliferation with respect to normal subjects or tissues, to detect the presence or absence of prostate cancer, or monitor treatment of prostate cancer in said patient.

A method for detecting the presence or absence of a skin disorder or monitoring a treatment of a skin disorder in a patient, said method comprising:

• a) administering deuterated water to said patient for a period of time sufficient for said deuterated water to label keratin in the skin of said patient;
• b) collecting a sample of said labeled keratin;
• c) measuring the content, rate of incorporation and/or pattern or rate of change in content and/or pattern of isotope labeling of said keratin;
• and
• d) comparing said rate or pattern to historical data, data obtained from a control subject, data obtained from non-disordered tissue in the same subject, data obtained from the same subject prior to treatment, or data obtained from the same subject prior to disorder onset in order to evaluate whether or not there is an increase or decrease in keratin synthesis with respect to normal subjects or tissues, to detect the presence or absence of a skin disorder or to monitor the treatment of a skin disorder.

A method for detecting the presence or absence of a colon disorder or monitoring a treatment of a colon disorder in a patient, said method comprising:

• a) administering deuterated water to said patient for a period of time sufficient for said deuterated water to label mucin in one or more colon epithelial cells in said patient;
• b) collecting a sample of stool or epithelial tissue or colon epithelial cells comprising said labeled mucin;
• c) measuring the content, rate of incorporation and/or pattern or rate of change in content and/or pattern of isotope labeling of said mucin in said colon epithelial cells;
• d) comparing said rate or pattern to historical data, data obtained from a control subject, data obtained from non-disorder tissue in the same subject, data obtained from the same subject prior to treatment, or data obtained from the same subject prior to disorder onset in order to evaluate whether or not there is an increase or decrease in mucin synthesis with respect to normal subjects or tissues, to detect the presence or absence of a colon disorder or monitor the treatment of a colon disorder.

A method for detecting the presence or absence of a colon disorder or monitoring a treatment of a colon disorder in a patient, said method comprising:

• a) administering deuterated water to said patient for a period of time sufficient for said deuterated water to label DNA in one or more colon epithelial cells in said patient thereby forming labeled colon epithelial cell DNA;
• b) collecting a sample of stool or tissue comprising said labeled colon epithelial cell DNA;
• c) measuring the content, rate of incorporation and/or pattern or rate of change in content and/or pattern of isotope labeling of said DNA in said colon epithelial cells;
• d) comparing said rate or pattern to historical data, data obtained from a control subject, data obtained from non-disorder tissue in the same subject, data obtained from the same subject prior to treatment, or data obtained from the same subject prior to disorder onset in order to evaluate whether or not there is an increase or decrease in colon epithelial cell proliferation with respect to normal subjects or tissues, to detect the presence or absence of a colon disorder or monitor the treatment of a colon disorder.