Chromosome Intrachanges and Interchanges Detected by Multicolor Banding in Lymphocytes: Searching for Clastogen Signatures in the Human Genome

Johannes, Christian; Horstmann, M.; Durante, Marco; Chudoba, Ilse; Obe, Günter

doi:10.1667/rr3157

Cited by 52 publications

(18 citation statements)

References 39 publications

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“…Our analysis is, of course, based only on the exchanges that are visible as colour junctions between parts of different chromosomes. Homologous pair interactions, intrachanges and exchanges below the limit of resolution would all tend toward an increase in overall complexity of the patterns described and colour-junctions detected (Singleton et al, 2002;Johannes et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…The application of multiple-colour FISH techniques is revealing the hither-to hidden complexities of radiation-induced chromosome aberrations Cornforth, 2001;Boei et al, 2002;Obe et al, 2002;Johannes et al, 2004). In particular, densely ionising radiation, such as high-linear energy transfer (LET) ·-particles are now known to result characteristically in the formation of complex chromosome aberrations (three or more breaks in two or more chromosomes) in a variety of cell types, even after exposure to very low doses corresponding to single-particle traversals (Savage and Simpson, 1994;Griffin et al, 1995;Anderson et al, 2000;Moquet et al, 2001).…”

confidence: 99%

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Increased complexity of radiation-induced chromosome aberrations consistent with a mechanism of sequential formation

Anderson¹,

Papworth²,

Stevens³

et al. 2005

Cytogenet Genome Res

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Complex chromosome aberrations (any exchange involving three or more breaks in two or more chromosomes) are effectively induced in peripheral blood lymphocytes (PBL) after exposure to low doses (mostly single particles) of densely ionising high-linear energy transfer (LET) α-particle radiation. The complexity, when observed by multiplex fluorescence in situ hybridisation (m-FISH), shows that commonly four but up to eight different chromosomes can be involved in each rearrangement. Given the territorial organisation of chromosomes in interphase and that only a very small fraction of the nucleus is irradiated by each α-particle traversal, the aim of this study is to address how aberrations of such complexity can be formed. To do this, we applied theoretical “cycle” analyses using m-FISH paint detail of PBL in their first cell division after exposure to high-LET α-particles. In brief, “cycle” analysis deconstructs the aberration “observed” by m-FISH to make predictions as to how it could have been formed in interphase. We propose from this that individual high-LET α-particle-induced complex aberrations may be formed by the misrepair of damaged chromatin in single physical “sites” within the nucleus, where each “site” is consistent with an “area” corresponding to the interface of two to three different chromosome territories. Limited migration of damaged chromatin is “allowed” within this “area”. Complex aberrations of increased size, reflecting the path of α-particle nuclear intersection, are formed through the sequential linking of these individual sites by the involvement of common chromosomes.

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Section: Discussionmentioning

confidence: 99%

Increased complexity of radiation-induced chromosome aberrations consistent with a mechanism of sequential formation

Anderson¹,

Papworth²,

Stevens³

et al. 2005

Cytogenet Genome Res

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show abstract

“…Besides, cytogenetic studies point to a much higher complexity in the chromosomal rearrangements induced by heavy ions compared to sparsely ionizing radiation (Figure 3) -i.e. rearrangements induced by heavy ions involve a higher number of chromosomes and breaks 47 , and include both intra-and inter-chromosomal exchanges 48,49 . Most of these complex rearrangements, however ultimately lead to cell death.…”

Section: Chromosomal Aberrationsmentioning

confidence: 99%

Heavy ion carcinogenesis and human space exploration

Durante¹,

Cucinotta²

2008

Nat Rev Cancer

510

324

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Prior to the human exploration of Mars or long duration stays on the Earth's moon, the risk of cancer and other diseases from space radiation must be accurately estimated and mitigated. Space radiation, comprised of energetic protons and heavy nuclei, has been show to produce distinct biological damage compared to radiation on Earth, leading to large uncertainties in the projection of cancer and other health risks, while obscuring evaluation of the effectiveness of possible countermeasures. Here, we describe how research in cancer radiobiology can support human missions to Mars and other planets. Introduction:

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“…On the contrary, most data point to few inversions compared to interchromosomal exchanges. Even using high-resolution mBAND FISH and densely ionizing radiation [Johannes et al, 2004] the F -ratio remains much higher than 1.…”

Section: F -Ratio and Clustered Breaksmentioning

confidence: 96%

DNA Double Strand Breaks and Chromosomal Aberrations

Obe

Durante

2010

Cytogenet Genome Res

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DNA double strand breaks (DSBs) are ultimate lesions for the formation of chromosomal aberrations (CAs). The formation of CAs is dependent on many factors; some of these are discussed in this review. FISH methodologies have uncovered CA types which cannot be seen with the classical staining methods, and thereby widened our understanding of the origin of CAs. The mobility of DSBs in interphase nuclei is limited. This makes it especially difficult to understand the origin of complex CAs involving many chromosomes. Even using high-resolution mBAND FISH to analyze CAs, the ratio of inter-/intrachromosomal CAs is higher than 1. From this it was postulated that only a subset of DSBs, namely, complex or clustered DSBs give rise mainly to interchromosomal CAs. The finding that endonucleases induce CAs does not fit the idea of complex DSBs being responsible for CA. Probably it is the proximity and not the complexity of DSBs which leads to CA.

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Chromosome Intrachanges and Interchanges Detected by Multicolor Banding in Lymphocytes: Searching for Clastogen Signatures in the Human Genome

Cited by 52 publications

References 39 publications

Increased complexity of radiation-induced chromosome aberrations consistent with a mechanism of sequential formation

Increased complexity of radiation-induced chromosome aberrations consistent with a mechanism of sequential formation

Heavy ion carcinogenesis and human space exploration

DNA Double Strand Breaks and Chromosomal Aberrations

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