PMID- 10477349 OWN - NLM STAT- MEDLINE DCOM- 19990922 LR - 20190702 IS - 0027-5107 (Print) IS - 0027-5107 (Linking) VI - 444 IP - 1 DP - 1999 Jul 21 TI - Cell cycle specificity of cytogenetic damage induced by 3,4-epoxy-1- butene. PG - 151-8 AB - 3,4-epoxy-1-butene (EB), a primary metabolite of butadiene, is a direct-acting "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 exposed at the G(0) stage of the cell cycle. To investigate whether repair of DNA lesions is responsible for the lack of cytogenetic responses seen after G(0) treatments, we used cytosine arabinoside (ara-C) to inhibit DNA polymerization during DNA repair. If enough repairable lesions are present, double-strand breaks should accumulate and form chromosome-type ("S-independent") deletions and exchanges. This is exactly what occurred. EB induced chromosome deletions and dicentrics at the first division following treatment, when the EB exposure was followed by ara-C. Without ara-C treatment, there was no induction of CAs. These experiments indicate that the relatively low levels 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 chromatid-type aberrations. FAU - Kligerman, A D AU - Kligerman AD AD - Genetics and Cellular Toxicology Branch, Mail Drop 68, Environmental Carcinogenesis Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. kligerman.andrew@epa.gov FAU - Doerr, C L AU - Doerr CL FAU - Tennant, A H AU - Tennant AH LA - eng PT - Journal Article PL - Netherlands TA - Mutat Res JT - Mutation research JID - 0400763 RN - 0 (Epoxy Compounds) RN - 0 (Mutagens) RN - 04079A1RDZ (Cytarabine) RN - 478ERR5NKR (3,4-epoxy-1-butene) RN - 9007-49-2 (DNA) SB - IM MH - Cell Cycle MH - Chromosome Aberrations MH - Cytarabine/pharmacology MH - DNA/biosynthesis/drug effects/genetics MH - DNA Repair/drug effects MH - Epoxy Compounds/*toxicity MH - Humans MH - In Vitro Techniques MH - Lymphocytes/cytology/drug effects/metabolism MH - Mutagens/*toxicity MH - Resting Phase, Cell Cycle MH - Sister Chromatid Exchange/drug effects EDAT- 1999/09/08 00:00 MHDA- 1999/09/08 00:01 CRDT- 1999/09/08 00:00 PHST- 1999/09/08 00:00 [pubmed] PHST- 1999/09/08 00:01 [medline] PHST- 1999/09/08 00:00 [entrez] AID - S1383571899000777 [pii] AID - 10.1016/s1383-5718(99)00077-7 [doi] PST - ppublish SO - Mutat Res. 1999 Jul 21;444(1):151-8. doi: 10.1016/s1383-5718(99)00077-7.