title: Cytogenetic evidence that DNA topoisomerase II is not involved in radiation induced chromsome-type aberrations.
abstract: ICRF-187 (Cardioxane™, Chiron) is a catalytic inhibitor of DNA topoisomerase II (Topo II), proposed to act by blocking Topo II-mediated DNA cleavage without stabilizing DNA-Topo II-"cleavable complexes". In this study ICRF-187 was used to evaluate the potential involvement of DNA topoisomerase II in the formation of the radiation-induced chromosome-type aberrations in the G0 phase of the cell cycle in human lymphocytes from three healthy male donors. This is based on many evidences that DNA topoisomerases are involved in DNA recombination, mainly of illegitimate type (non-homologous) both in vitro and in vivo. The results obtained clearly indicated that ICRF-187 did not induce per se any chromosomal damage. When challenged with the non-catalytic Topo II poison VP-16 (etoposide), which acts by stabilizing the "cleavable complex" generating "protein concealed" DSB's and thus chromosomal aberrations, it completely abolished the significant induction of chromosome-type aberrations and formation of dicentric chromosomes. This indicates that ICRF-187 acts effectively as catalytic inhibitor of Topo II. On the other hand, when X-ray treatments were challenged with ICRF-187 using experimental conditions as for VP-16 treatments, no modification of the incidence of chromosome-type aberrations and dicentric chromosomes was observed. On this basis, we conclude that Topo II is not involved in the formation of X-ray-induced chromosome-type aberrations and dicentric chromosomes in human lymphocytes in the G0 phase of the cell cycle.
authors.affiliation: Dipartimento di Scienze Ecologiche e Biologiche, Università degli Studi della Tuscia, Largo dell'Università s.n.c., 01100 Viterbo, Italy. Electronic address: mosesso@unitus.it.
authors.forename: P
authors.initials: P
authors.lastname: Mosesso
authors.affiliation: Dipartimento di Scienze Ecologiche e Biologiche, Università degli Studi della Tuscia, Largo dell'Università s.n.c., 01100 Viterbo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pepe
authors.affiliation: Dipartimento di Scienze Ecologiche e Biologiche, Università degli Studi della Tuscia, Largo dell'Università s.n.c., 01100 Viterbo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ottavianelli
authors.affiliation: Dipartimento di Scienze Ecologiche e Biologiche, Università degli Studi della Tuscia, Largo dell'Università s.n.c., 01100 Viterbo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Schinoppi
authors.affiliation: Research Toxicology Centre, Via Tito Speri 12/14, 00040, Pomezia, Roma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cinelli
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations / Q000187:drug effects*; D002877:Chromosomes, Human / Q000187:drug effects / Q000528:radiation effects*; D020732:Cytogenetic Analysis; D059766:DNA End-Joining Repair / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D064730:Dexrazoxane / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects; D008297:Male; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*; D014965:X-Rays
chemical_list: D059005:Topoisomerase II Inhibitors; D064730:Dexrazoxane; D005047:Etoposide; D004250:DNA Topoisomerases, Type II
keywords: Chromosome-type aberrations; DNA double strand breaks (DSB); DNA topoisomerase II inhibitors; ICRF-187; Non homologous end joining recombination (NHEJR); X-ray induced chromosomal aberrations