BLEOMYCIN SULFATE-INDUCED MICRONUCLEI IN HUMAN, RAT, AND MOUSE PERIPHERAL-BLOOD LYMPHOCYTES

The sensitivity to micronucleus (MN) induction of human, mouse, and ra t peripheral blood lymphocytes (PBLs) exposed to bleomycin sulfate (BL M) in vitro was compared in cytochalasin B-induced binucleated (BN) ce lls. For the PBLs of each species, either 0, 5, 10, 20, 40, 60, 80, or 160 mu g/ml BLM was added to 5 mi aliquots of whole blood for 4 hr at 37 degrees C in a 5% CO2 atmosphere. Leukocytes were isolated on a de nsity gradient and cultured in the presence of phytohemagglutinin to s timulate blastogenesis, and cytochalasin B was added to each culture a t 21 hr postinitiation to prevent cytokinesis. A total of 4,000 BNs/co ncentration/species was analyzed for MN in two independent experiments . In addition, multiple-MN-BNs were quantitated, and the nucleation in dex was determined. Significant increases both in total MN-BNs and mul tiple-MN-BNs were observed at all concentrations in all species. All t hree species' concentration-response curves gave good fits (r(2) valve s from 0.87 to 0.95) to either a linear or a square root model (y = mx + b or y = m[x](0.5) + b, respectively; where y = the percentage of M N-BN, m is the slope, and b is the y-intercept). The MN induction in t he human and rat PBLs was not statistically different, but both were s ignificantly less sensitive than the response shown by the BLM-exposed mouse PBLs. This difference in MN susceptibility was observed only at BLM test concentrations greater than or equal to 20 mu g/ml. The nucl eation index was significantly decreased in all species at either 80 o r 160 mu g/ml. (C) 1995 Wiley-Liss, Inc.