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-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.
Kligerman
A D
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
Doerr
C L
CL
Tennant
A H
AH
D002453:Cell Cycle; D002869:Chromosome Aberrations; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects; D004852:Epoxy Compounds / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D016192:Resting Phase, Cell Cycle; D012854:Sister Chromatid Exchange / Q000187:drug effects
D004852:Epoxy Compounds; D009153:Mutagens; D003561:Cytarabine; C024370:3,4-epoxy-1-butene; D004247:DNA