PMID- 9222108 OWN - NLM STAT- MEDLINE DCOM- 19970918 LR - 20191102 IS - 0196-4763 (Print) IS - 0196-4763 (Linking) VI - 28 IP - 3 DP - 1997 Jul 1 TI - Flow cytometric analysis of micronucleus induction in rat bone marrow polychromatic erythrocytes by 1,2;3,4-diepoxybutane, 3,4-epoxy-1-butene, and 1,2-epoxybutane-3,4-diol. PG - 228-35 AB - Automation of the analysis of micronucleus induction with flow cytometry was developed by using mouse bone marrow or peripheral blood. In the present study, we report the use of flow cytometry for the identification and quantification of micronuclei (MN) induced in rat bone marrow polychromatic erythrocytes. Three metabolites of the industrial chemical 1,3-butadiene, namely 1,2;3,4-diepoxybutane (DEB), 3,4-epoxy-1-butene (EB) and 1,2-epoxybutane-3,4-diol (diol-EB), were studied in addition to mitomycin C and cyclophosphamide, which served as positive controls. DEB showed a dose-dependent increase in the frequency of MN, whereas EB was completely negative and diol-EB only weakly positive at one dose level. The effect of the positive control compounds was observed 48 h after a single injection in a dose-dependent manner. Flow cytometry was an effective method to quantitate bone marrow MN induction in the rat when density gradient separation of polychromatic erythrocytes is used. The results are compatible with the theory that oxidation of EB to the mutagenic metabolite DEB occurs at a low rate in rat bone marrow and that EB is detoxified by epoxide hydrolase and by conjugation with glutathione by glutathione transferase yielding nonmutagenic metabolites. Thus, the reported lack of MN induction by 1,3-butadiene inhalation in rat bone marrow is explained. FAU - Lahdetie, J AU - Lahdetie J AD - Department of Medical Genetics, University of Turku, Finland. FAU - Grawe, J AU - Grawe J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cytometry JT - Cytometry JID - 8102328 RN - 0 (Benzimidazoles) RN - 0 (Epoxy Compounds) RN - 0 (Fluorescent Dyes) RN - 0 (Glycols) RN - 0 (Mutagens) RN - 17177-50-3 (3,4-epoxybutane-1,2-diol) RN - 478ERR5NKR (3,4-epoxy-1-butene) RN - 60OB65YNAB (diepoxybutane) RN - P976261J69 (bisbenzimide ethoxide trihydrochloride) SB - IM MH - Animals MH - Benzimidazoles MH - *Bone Marrow Cells MH - Cell Separation MH - Epoxy Compounds/toxicity MH - Erythrocyte Aging MH - Erythrocytes/cytology/*drug effects MH - Flow Cytometry/*methods MH - Fluorescent Dyes MH - Glycols/toxicity MH - Male MH - Mice MH - *Micronucleus Tests MH - Mutagens/toxicity MH - Rats MH - Rats, Sprague-Dawley EDAT- 1997/07/01 00:00 MHDA- 2000/06/20 09:00 CRDT- 1997/07/01 00:00 PHST- 1997/07/01 00:00 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1997/07/01 00:00 [entrez] AID - 10.1002/(SICI)1097-0320(19970701)28:3<228::AID-CYTO7>3.0.CO;2-9 [pii] AID - 10.1002/(sici)1097-0320(19970701)28:3<228::aid-cyto7>3.3.co;2-j [doi] PST - ppublish SO - Cytometry. 1997 Jul 1;28(3):228-35. doi: 10.1002/(sici)1097-0320(19970701)28:3<228::aid-cyto7>3.3.co;2-j.