CELL-FREE DNA IN HUMAN BLOOD-PLASMA - LENGTH MEASUREMENTS IN PATIENTSWITH PANCREATIC-CANCER AND HEALTHY CONTROLS

The amount of non-cell-associated DNA free in blood plasma from pancre atic cancer patients usually exceeds that from healthy donors. We have evaluated the plasma DNA by gel electrophoresis and measured the vari ation in length of soluble DNA fragments by electron microscopy in pla sma from three patients with pancreatic cancer and from three healthy controls. Whereas electrophoresis of nick-translated DNA isolated from plasma obtained from healthy controls showed autoradiographic bands a t sizes equivalent to whole-number multiples (1-5x) of nucleosomal DNA (185-200 bp), in the samples obtained from pancreatic cancer patients , stronger ladder patterns appeared. Likewise, strand length distribut ions of DNA (DNA-SL) in the two groups differ. The DNA-SL distribution data include 2,752 measurements made from cancer patient plasma and 3 ,291 for control plasma. The shortest DNA-SL measured similar to 30 nm (similar to 88 bp calculated at 0.34 nm/bp) and the largest similar t o 28,000 nm (>80,000 bp), with 50% of all lengths measuring between 10 0 and 900 nm long. The average plasma DNA-SL in controls (311 nm; medi an, 273 nm) exceeded that in cancer patients (231 nm; median, 185 nm). Small excesses of DNA at similar to 63, similar to 126, similar to 18 9, similar to 252, and similar to 315 nm, corresponding to small multi ples of lengths associated with nucleosomes, were more prominent in th e cancer patient plasma than in the healthy control plasma. This study provides evidence indicating differences in non-cell-associated DNA i n plasma between cancer patients and healthy controls and indicates th at a significant amount of this DNA is probably derived from apoptosis in neoplastic and/or normal cells.