A Traceable Cancer Model: DNA Damage, Fragile Site-SMGs, Mitotic Slippage, 4n-Genome-Reduction to Fitness-Gained, Initiating, 2n First Cells

We have known since 1976 that cancer evolves clonally from one initiated normal human cell, the first cell. Today we see that this fact has been overshadowed from federal funding choice of the mutation theory (MT), which not yet has shown tumorigenesis-initiation in normal human cells. Our suggested, death signaled, stress model from time delayed S-period (replication slowness), causing repair instability from under-replicated lesions in repetitive DNAs, herein has the objective of revealing, significant literature support from a mini-review. We reasoned that early versus late S-period stress would have different outcomes: early the slowness affecting mitotic slippage with diploid re-replication to 4n cells whereas late-S, with milder stress effect, producing diploid cells. In cancer burden, near-half is diploid, but tetraploid solid tumors have the attention. The initial 4n cells were special with orderly genomic reductive division to diploid first cells with measurable fitness-gain from hours-reduced total cell cycle time. Experimental data from Coxsakie-B3 virus infected normal fibroblasts, reiterated 4n cell production from death-signaled recovery-cells with progressive cell-phenotypic changes to polygonal and roundness cell-shapes, indistinguishable from diagnostic/prognostic cancer morphology. The 4n cells showed a self-inflicted 90° turn of the 4n nucleus before division, affecting a perpendicular orientation of the fitness-gained first cells relative to neighboring cells. In an illustrated cell cycle drawing with early and late S-period stress, it became clear that coding genes on borders of repair unstable satellite, repetitive DNA regions, could become mutated. We found these mutations to be tumor SMGs (significantly mutated genes). Evidential material was presented for loss of function genetics driving tumorigenesis to a parasitic lifestyle.

Dynamics of Tetrahmpena macronuclear lamina during cell division

During mitosis, the nuclear lamina in higher eukaryotic cells undergoes a distinctly morphological change.It breaks down into lamin polymers or monomers at prophase. At telophase, the lamins reassemble around the condensed chromatin to form the layer of lamina. Using antiserum to mammalian lamins, we studied the dynamics of lamina during cell division in the macronuleus of Tetrahymena shanghaiensis, which divided in the way of amitosis. In contrast to those in higher animal cells, the typical perinuclear lamin distribution in the macronucleus persisted throughout the whole cell cycle. It was further found that in some synchronized cells, the lamin distribution displayed an unusual pattern consisting of a series of spots within the macronucleus. Using South-western hybridization, we found that the purified 66 KD lamin in Tetrahymena showed specific affinity with the telomere DNA sequence in the same species. Therefore, we propose that pattern of immunofluorescence may be due to the interaction of lamin protein with the nucleoli and the condensed chromatins in the macronucleus.

Observation of two amitotic ways in the epidermal cells of plant Pelargonium zonale ‘Kleiner Liebling＇-Amitotic nuclear division for endoreduplicated cells

Amitosis, different from mitosis, is a rare form of the proliferation of the cells. Most amitosis were observed in animal cells; only few of them were reported in plant cells. The cytological investigation in this study demonstrated first time in Pelargonium zonale two different amitotic nuclear division ways： cleavage and constriction, in which no appearance of the visible chromosomes and no spindles were observed. After amitotic nuclear division the cytokinesis was also observed, in which the cytoplasm divided directly into two or more parts accompany with formation of two or more daughter cells. This study showed the genetic material may sometimes be unequally distributed between the daughter cells in amitosis, and the amitosis could lead to bi-, tri- and multinucleated cells. These new findings are discussed in regard to the nuclear amitotic process in polyploid cells which gives rise to smaller, viable nuclei in multinucleated cells with reduced numbers of genomes. It was suggested that amitosis could be a way of the division of the endoreduplicated cells.