[Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006]
Epidemiology/Lifestyle Factors: Diet and Cancer 1
The early cancer-associated epigenetic DNA hypomethylation induces the target morphological involution pericentromeric/centromeric heterochromatin in tumorigenesis.
Ludmila P. Shvachko
Institute of Molecular Biology and Genetics, Kiev, Ukraine
We are study the cancer type somatic mutagenesis in tumorigenesis to elucidate the interrelationship in cancer development and cancer prevention mechanisms. The striking correlation between early cancer-associated pattern genome DNA hypomethylation, the target pericentromeric/centromeric heterochromatin decondensation and the somatic chromosomal aneuploidy causal link in tumorigenesis we have observed. But why the cancer somatic cell becomes dramatic tolerantly to the aneuploidy formation? We should have concepted that the highly methyl-density constitutive heterochromatin organization major as the mitotic pericentromeric/centromeric heterochromatin is the suprete epiregulon which responsible for the preservation of pivotal somatic cell diploidy stability which incompatible with aneuploidy formation. So, we have revealed the striking correlation between the progressive loss of the cancer somatic dyploidity and the DNA hypomethylation induced constitutive heterochromatin morphological alterations in the mitotic lymphocytes from the solid cancer patients. Have been shown that the cancer-associated pattern DNA hypomethylation causal linked with not only constitutive heterochromatin decondensation but also with the its consequent morphological involution on the latent polytenization way as the target metaphase chromomerization and interphase heterochromatinization by Gimsa and DAPI / Hoechst 33258 quantitative fluorescent analysis was shown. The significant extrareplication of the amplified heterochromatin DNA by the DIG-pUCI19(Alu) hybridization analysis was confirmed. Moreover we revealed the double metaphase chromosome formation mechanisms during the cancer somatic mutagenesis by the target endoreduplication and the ectopic conjugation of the mitotic homology sister chromatids. The 5`-azacytidine inhibition of the pattern genome DNA methylation and the mitotic pericentromeric/centromeric heterochromatin condensation causal linked with the target interphase heterochromatinization by the heterochromatin DNA extrareplication mechnisms was confirmed. Thus on the base of our studies have been concluded that the general pattern somatic genome DNA hypomethylation/demethylation phenomenon creates the trigger conditions for the pre-carcinogenesis development by the dramatic mitotic constitutive heterochromatin latent morphological polyteny involution directly connected with major loss of the somatic diploidity and somatic aneuploidy opportunity in tumorigenesis. We have been assumed that the cancer pattern genome DNA methylation supportion and anti- DNA -demethylation treatments may be the general new strategies for the long-term efficacy in supression of the cancer somatic biology and the neoplasia prevention.
Copyright © 2006 by the American Association for Cancer Research.