Common fragile sites on human chromosomes represent transcriptionally active regions: evidence from camptothecin.
Cellular processes involved in the expression of fragile sites (FS) have been investigated by studying the possible modulation of their induction by camptothecin, a specific topoisomerase I inhibitor. Expression of FS was induced by aphidicolin and then camptothecin was administered to cultures during G2 phase. Under these conditions, a very high number of chromosome aberrations were obtained: R-bands carrying FS were specifically involved in breakage and, in particular, the common FS (cFS) bands already expressed in aphidicolin-treated cultures were the most affected. These data show that the expressed FS are preferential targets of camptothecin, that is, regions where topoisomerase I-cleavable complexes are formed. This allows us to hypothesize that cFS could represent the cytogenetic expression of transcriptionally active regions. These treatments were able to induce, besides the known FS, four new FS, namely 1p34, 6p21, 6q25, and 15q15.
Sbrana
I
I
Dipartimento di Scienze dell'Uomo e dell'Ambiente, Università di Pisa, Italy.
Zavattari
P
P
Barale
R
R
Musio
A
A
D000328:Adult; D016590:Aphidicolin / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology*; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects; D019457:Chromosome Breakage / Q000235:genetics; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002877:Chromosomes, Human / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D059004:Topoisomerase I Inhibitors; D014158:Transcription, Genetic / Q000187:drug effects*
D002843:Chromatin; D059004:Topoisomerase I Inhibitors; D016590:Aphidicolin; D002166:Camptothecin