title: Bleomycin sulfate-induced micronuclei in human, rat, and mouse peripheral blood lymphocytes.
abstract: The sensitivity to micronucleus (MN) induction of human, mouse, and rat peripheral blood lymphocytes (PBLs) exposed to bleomycin sulfate (BLM) in vitro was compared in cytochalasin B-induced binucleated (BN) cells. For the PBLs of each species, either 0, 5, 10, 20, 40, 60, 80, or 160 micrograms/ml BLM was added to 5 ml aliquots of whole blood for 4 hr at 37 degrees C in a 5% CO2 atmosphere. Leukocytes were isolated on a density gradient and cultured in the presence of phytohemagglutinin to stimulate blastogenesis, and cytochalasin B was added to each culture at 21 hr postinitiation to prevent cytokinesis. A total of 4,000 BNs/concentration/species was analyzed for MN in two independent experiments. In addition, multiple-MN-BNs were quantitated, and the nucleation index was determined. Significant increases both in total MN-BNs and multiple-MN-BNs were observed at all concentrations in all species. All three species' concentration-response curves gave good fits (r2 values 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 MN-BN, m is the slope, and b is the y-intercept). The MN induction in the human and rat PBLs was not statistically different, but both were significantly less sensitive than the response shown by the BLM-exposed mouse PBLs. This difference in MN susceptibility was observed only at BLM test concentrations > or = 20 micrograms/ml. The nucleation index was significantly decreased in all species at either 80 or 160 micrograms/ml.
authors.affiliation: Novel Pharmaceutical, Inc., Research Triangle Park, NC 27709.
authors.forename: G L
authors.initials: GL
authors.lastname: Erexson
authors.forename: M F
authors.initials: MF
authors.lastname: Bryant
authors.forename: P
authors.initials: P
authors.lastname: Kwanyuen
authors.forename: A D
authors.initials: AD
authors.lastname: Kligerman
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015162:Micronucleus Tests; D009153:Mutagens; D051381:Rats
chemical_list: D009153:Mutagens; D001761:Bleomycin