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Chromatin, Nuclei and Water: Alterations and Mechanisms for Chemically- Induced Carcinogenesis

  • C. Nicolini
  • G. Brambilla
  • F. Beltrame
  • S. Capitani
  • P. Carlo
  • B. Cavazza
  • A. Chiabrera
  • R. Finollo
  • M. Grattarola
  • A. Manzoli
  • N. Maraldi
  • A. Martelli
  • G. Parodi
  • E. Patrone
  • S. Ridella
  • V. Trefiletti
  • R. Viviani
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 52)

Abstract

In recent years experimental evidences (1–5) have been accumulating on the orderly organization of the chromatin-DNA within mammalian cells from the Watson-Crick double helix (secondary structure) through successive higher order DNA foldings (nucleosome and super-nucleosome) up to a quinternary level (5), being postulated as drapery-like regular packing of 300 A° “solenoid-like” or “rope-like” fibers. While uncertainty still exists on the exact three-dimensional geometry ‘in situ’ of the latter two superstructures, there is general agreement on both the tertiary structure (wrapping of DNA around octamer histones to form the nucleosome) and on the modulation of the overall chromatin structure during cell transformation and cell proliferation. Namely the native higher order structure (5, 6, 7,) has been conclusively linked to DNA replication and mitotic condensation, through abrupt structural transitions induced by enzymatic modifications of HI histones, ions and generally by the neutralization of DNA phosphate charge (as strikingly expected from polyelectrolyte theory (8)). An increase of chromatin condensation has been also consistently associated with cell transformation (either induced by virus, chemical or spontaneously), suggesting that an higher order chromatin superpacking and a reduced chromatin template (9, 4) are a prerequisite for the expression of the transformed phenotype. This apparent paradox is however complicated by the significant chromatin modulation occuring during cell cycle progression of both normal and transformed cells, which obscure the increased condensation. It would seem indeed that only the degree of coupling between changes in nuclear morphometry (chromatin higher order structure) and changes in cell morphometry is uniquely low for individual transformed cell, being quite high for every fibroblast or normal cell (5, 10). In transformed cell, the absence of any coupling would let chromatin to progress through its cycles of condensation and decondensation regardless the shape assumed by the intact cell, including a round one as in suspension or as induced by cell-cell interaction, nutritional deprivation or cell-substrate interaction. The mechanism by which cell geometry and cell growth are respectively coupled in normal and uncoupled in transformed cells (10) was indeed suggested to be the physically (microtubules-microfilaments) or chemically induced coupling and uncoupling between nuclear morphometry and cell geometry, with the higher degree of fiber superpacking being also related to the expressions of transformed phenotypes. It would be then interesting to verify if these findings can be generalized to cell transformation induced by chemical carcinogens in VIVO, but prior to characterize its significance and specific structural-functional modification induced by chemical carcinogens (as originally reported time ago (11)), it is mandatory to know more about chromatin itself. Unperturbed rat liver cells and rat liver chromatin were mainly used as experimental models; for the purpose of comparison complementary measurements on calf thymus chromatin have been carried out.

Keywords

Chromatin Structure Partial Hepatectomy Acridine Orange Chemical Carcinogen Integrate Optical Density 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • C. Nicolini
    • 1
    • 2
    • 3
  • G. Brambilla
    • 1
    • 2
    • 3
  • F. Beltrame
    • 2
    • 2
    • 3
  • S. Capitani
    • 1
    • 2
    • 3
  • P. Carlo
    • 1
    • 2
    • 3
  • B. Cavazza
    • 1
    • 2
    • 3
  • A. Chiabrera
    • 1
    • 2
    • 3
  • R. Finollo
    • 1
    • 2
    • 3
  • M. Grattarola
    • 1
    • 2
    • 3
  • A. Manzoli
    • 2
    • 2
    • 3
  • N. Maraldi
    • 1
    • 2
    • 3
  • A. Martelli
    • 1
    • 2
    • 3
  • G. Parodi
    • 1
    • 2
    • 3
  • E. Patrone
    • 1
    • 2
    • 3
  • S. Ridella
    • 1
    • 2
    • 3
  • V. Trefiletti
    • 1
    • 2
    • 3
  • R. Viviani
    • 1
    • 2
    • 3
  1. 1.Interdisciplinary Group of BiostructureUniversity of GenovaItaly
  2. 2.National Research CouncilItaly
  3. 3.Department of Biophysics and PhysiologyTemple UniversityPhiladelphiaUSA

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