Detection of a serum DNA-binding protein associated with cancer.

An accompanying report describes the purification and partial characterization of a unique DNA-binding protein (Mr 64,000; pI 5.9) that is present in human sera. This report gives the results of assays of sera from patients for the bleomycin inhibitor protein (BIP) using the Pseudomonas bacteriophage covalently closed circular DNA fluorescence technique standardized for DNA breakage induced by bleomycin. The results of the BIP assays were expressed by values of specific activity of inhibition. One arbitrary unit of inhibitory activity was defined as equivalent to the amount of serum protein required to cause 50% inhibition of DNA degradation using standard conditions of the DNA breakage assay. The mean values of specific activity of inhibition (SAI) for groups of healthy individuals (n = 26), patients with nonmalignant diseases (n = 33), and patients with malignant diseases (n = 83) were 12.60 +/- 4.69 (S.E.), 12.53 +/- 3.17, and 2.40 +/- 0.84 units/mg, respectively. Mean SAI values for patients with cancers of various types were: solid tumors (n = 46), 2.44 +/- 0.86; leukemias (n = 24), 2.59 +/- 0.96; and lymphomas (n = 18), 2.07 +/- 0.64. The decrease in BIP activity was not correlated with sex, age, or prior chemotherapy. Mean SAI values of male (n = 29) and female (n = 59) patients with cancer were 2.61 +/- 0.87 and 2.30 +/- 0.83 units/mg, respectively. Mean SAI values for different age groups were: 0 to 40 years (n = 21), 2.05 +/- 0.68 units/mg; 41 to 70 years (n = 56), 2.59 +/- 0.68 units/mg; and greater than 70 years (n = 11), 2.12 +/- 0.67 units/mg. Cancer patients with and without prior chemotherapy had mean SAI values of 2.97 +/- 0.85 (n = 23) and 2.20 +/- 0.86 units/mg (n = 65), respectively. Linear regression analysis comparing SAI values and serum protein levels showed no correlation (r = 0.21). These results suggest the decrease of the BIP is associated with malignant disease. Additional controlled studies are required before the significance of this association can be adequately assessed.