Biochemical Mediators and Mechanisms Involved in Chromatin Conformational Remodeling through the Cell Cycle.

Chromatin undergoes structural remodeling through the cell-cycle stages. Remodeling of the chromatin structure is extremely important for events occurring during these stages. The five major levels of structural organization, from the double-strand structure to the metaphase chromosomes are possible due to specific factors and mechanisms that function in synchrony. The mitotic promoting factors, the "structural maintenance of chromosomes" proteins, and proteins associated with cytoskeletal and nucleoskeletal elements have specific roles in structural modeling and functioning of DNA. It is of interest that the DNA decondensation cycle opposes the DNA condensation cycle. However, it is not clear if the factors and mechanisms involved in the DNA decondensation cycle are exactly opposite to the DNA condensation cycle. Also interesting is that chromosome-specific chromatin is positioned in the interphase nucleus in specific "territories" or "niches," a phenomenon similar to the exactly positioned genes at specific locations on a fully condensed chromosome. We review the factors and mechanisms in remodeling chromatin, maintaining structural integrity at each organizational level, and impact of this structural remodeling on functions of the genetic material.

Bleomycin-induced genotoxicity in vitro in human peripheral blood lymphocytes evidenced as complex chromosome- and chromatid-type aberrations.

Bleomycin is a chemotherapeutic and a radiomimetic drug which induces single and double-strand breaks in DNA by forming free radicals. We demonstrate in this study the capacity of bleomycin in inducing complex chromosome- and chromatid-type aberrations. Human peripheral blood was exposed to different concentrations of bleomycin (0, 10, 20, 30 and 40 µg/mL) and the aberrations induced were studied. The chromosomal-type aberrations studied were dicentrics, tricentrics, tetracentrics, centric rings and acentric fragments. The chromatid-type aberrations studied were double minutes, terminal lesions and terminal deletions. Though the overall trends that we obtained in the dose-dependent mitotic index and the chromosome- and chromatid-type aberrations conform to the reported literature, we could observe enhanced numbers and the types of such damages in this study. We could notice that chromosome-type aberrations were more than the chromatid-type aberrations. The enhanced numbers and the types of aberrations induced pave way for enhancing the sensitivity of genotoxic assays. Also, with more numbers and type of aberrations available, it would be useful to study the mechanisms of genotoxicity of drugs and in understanding phenomena such as "tolerance induction" to chronic exposure to such mutagens.

Prophasing interphase chromatin for assessing genetic damages-The evolution, applications and the future prospects.

Premature chromosome condensation (PCC) involves induction of near-chromosome-like morphology to interphase chromatin. Experimental induction of PCC was achieved by somatic cell hybridization (SCH), an approach which evolved into a chemical-induction process. PCC presents most probably the only way in which cytogenetic assessment of damages can be analyzed in special situations such as availability of limited numbers of sample cells and for cells which have lost their ability to divide. Initial experiments on PCC were reported in late 1960s and the technique has evolved into one with wide range of applications owing to its increased efficiency in detecting primary DNA damages. Biodosimetry remains as the primary area which utilizes PCC technique to the maximum efficiency with several multiple-groups participating in collaborative exercises for biodosimetric applications. However, in spite of the advantages that the technique offers, it is yet to reach its full potential. This is due to the inherent limitations of the manner in which PCC is induced currently; by the somatic cell hybridization and chemical-induction processes. An approach which combines these two would sure help in taking PCC to its highest potential as the preferred technique for assessment of primary DNA damages. We present the chronological events of evolution of the PCC technique along with its applications. Also, the limitations of the technique along with the suggestions for further refinement of the PCC technique are discussed.