A human platelet-derived inhibitor of unscheduled DNA synthesis in resting lymphocytes

We have examined the possibility of using heparinized whole human blood samples to estimate individual levels of unscheduled DNA synthesis (UDS). The unscheduled incorporation of tritiated thymidine into the DNA from the cells in whole blood treated for 20 h with 20--100 microM doses of N-acetoxy-2-acetylaminofluorene (NA-AAF) was inhibited over the levels of UDS calculated in platelet-depleted whole blood treated with NA-AAF in the same manner. A platelet-derived inhibitor of UDS in the mononuclear blood cell fraction (resting lymphocytes) was characterized (a) as requiring about 17.5 x 10(6) platelets to inhibit UDS in 1 x 10(6) lymphocytes; (b) as being released without direct platelet contact to lymphocytes; (c) as not being identified as one of the well known platelet release factors such as cyclic AMP, cyclic GMP, sodium arachidonate, CaCl2, ADP or prostaglandin E1; (d) as apparently being stored in platelets as a stable product since it could be found in a physiological saline lysate from platelets; and finally (e) as inhibiting semi-conservative DNA synthesis in lymphocytes as effectively as it does UDS.