Journal Article

The clastogenic response of the 1q12 heterochromatic region to DNA cross-linking agents is independent of the Fanconi anaemia pathway

E. Callén, M.J. Ramírez, A. Creus, R. Marcos, S. Frias, B. Molina, I. Badell, T. Olivé, J.J. Ortega and J. Surrallés

in Carcinogenesis

Volume 23, issue 8, pages 1267-1271
Published in print August 2002 | ISSN: 0143-3334
Published online August 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.8.1267
The clastogenic response of the 1q12 heterochromatic region to DNA cross-linking agents is independent of the Fanconi anaemia pathway

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Fanconi anaemia (FA) is a rare genetic syndrome of cancer susceptibility characterized by spontaneous and induced chromosome fragility, especially after treatment with cross-linking agents. Recent investigations showed interactions between FA proteins and chromatin remodelling factors. To investigate a potential uneven distribution of the FA pathway through the human genome depending on chromatin conformation, we have analysed chromosome breakage in the largest constitutively heterochromatic region in the human genome, the 1q12 band, in lymphocytes from FA patients, carriers and healthy controls after treatment with the cross-linking agents mitomycin-C (MMC) and diepoxybutane (DEB). As expected, a higher level of MMC-induced cytotoxicity and chromosome breakage was observed in cells from FA patients when compared with normal controls and carriers. However, the increase in 1q12 breakage after increasing concentrations of MMC was of a similar magnitude in FA patients, carriers and controls. Similarly, DEB induced a high level of overall genome chromosome fragility in cells from FA patients when compared with controls with no parallel increase in chromosome breaks specifically involving the heterochromatic band 1q12. We therefore conclude that, unlike the overall genome, the sensitivity of chromosome 1 constitutive heterochromatin to the chromosome breaking activity of cross-linking agents is independent of a functional FA pathway, indicating that the action of the FA pathway is unevenly distributed through the human genome.

Keywords: Cyt-B, cytochalasin-B; DEB, diepoxybutane; FA, Fanconi anaemia; MMC, mitomycin-C; MN, micronuclei; TL-FISH, tandem labelling fluorescence in situ hybridization

Journal Article.  3526 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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