Cell cycle specificity of cytogenetic damage induced by 3,4-epoxy-1-butene

3,4-Epoxy-1-butene (EB), a primary metabolite of butadiene, is a direct-act ing "S-dependent" genotoxicant that can induce sister chromatid exchanges ( SCEs) and chromosome aberrations (CAs) in cycling cells in vitro. However, EB is almost inactive when splenic or peripheral blood lymphocytes are expo sed at the G(0) stage of the cell cycle. To investigate whether repair of D NA lesions is responsible for the lack of cytogenetic responses seen after G(0) treatments, we used cytosine arabinoside (ara-C) to inhibit DNA polyme rization during DNA repair. If enough repairable lesions are present, doubl e-strand breaks should accumulate and form chromosome-type ("S-independent" ) deletions and exchanges. This is exactly what occurred. EB induced chromo some deletions and dicentrics at the first division following treatment, wh en the EB exposure was followed by ara-C. Without ara-C treatment, there wa s no induction of CAs. These experiments indicate that the relatively low l evels of damage induced by EB in G(0) lymphocytes are removed by DNA repair prior to DNA synthesis and thus, before the production of SCEs or chromati d-type aberrations. (C) 1999 Elsevier Science B.V. All rights reserved.