FREE DNA IN SERUM OF CANCER-PATIENTS AND EFFECT OF THERAPY

  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (3) , 646-650
Abstract
A radioimmunoassay for nanogram quantities of DNA was developed. [125I]Iododeoxyuridine-labeled DNA was used as the antigen, and the serum of a lupus erythematosus patient served as the source of antibody. The level of free DNA in the serum of 173 patients with various types of cancer and 55 healthy individuals was determined by this radioimmunoassay. DNA concentration in controls had a range of 0-100 ng/ml with a mean of 13 .+-. 3 ng/ml (SE). For comparison purposes, the range of 0-50 ng/ml was designated as normal, and 93% of controls were found in this range. In cancer patients, the DNA concentration ranged from zero to microgram levels with a mean of 180 .+-. 38 ng/ml. Fifty percent of the patient''s values were found in the range of 0-50 ng/ml. The other 50% were between 50 and 5000 ng/ml. No correlation could be seen between DNA levels and the size or location of the primary tumor. Significantly higher DNA levels were found in the serum of patients with metastatic disease (mean of 209 .+-. 39 ng/ml), as compared to nonmetastatic patients (mean 100 .+-. 30, P < 0.02). After radiation therapy in lymphoma, lung, ovary, uterus and cervical tumors, the levels decreased in 66-90% of the patients; in glioma, breast, colon and rectal tumors, the DNA levels decreased only in 16-33% of the patients. The decrease in DNA concentration in the serum correlated with improved clinical condition, such as decrease of tumor size and reduction of pain. When DNA levels increased or remained unchanged, a lack of response to treatment was noted. Of 17 patients who died within a year, 13 showed DNA levels that remained high or unchanged; only 4 showed lower levels during treatment. Persistent high or increasing DNA levels in the circulation may signal a relapse and are probably a poor prognostic sign. The relatively high percentage (50%) of cancer patients with apparently normal DNA levels would suggest that this test may have low diagnostic value. All these patients represent a selected group considered for radiation therapy, usually after surgery and/or chemotherapy. It is possible that a better correlation between DNA levels and cancer will be obtained prior to the initiation of treatment. DNA in the serum may be an important tool for the evaluation of therapy or the comparison of different regimens.

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