Neoplastic-Like CELL Changes of Normal Fibroblast Cells Associated with Evolutionary Conserved Maternal and Paternal Genomic Autonomous Behavior (Gonomery)

Abstract

The present comparative review discusses conservation of early evolutionary, relic genetics in the genome of man, which determine two different mechanistic reductive division systems expressed by normal, human diploid cells. The divisions were orderly and segregated genomes reductively to near-diploid daughter cells, which showed gain of a proliferative advantage (GPA) over cells of origin. This fact of GPA expression is a fundamental requirement for initiation of tumorigenesis. The division systems were responses to a carcinogen-free induction system, consisting of short (1 -3 days) exposures of young cells to nutritional deprivation of amino acid glutamine (AAD). In recovery growth (2 -4 days) endo-tetra/ochtoploid cells and normal diploid metaphase cells demonstrated chromosomal reductive divisions to respectively heterozygous and homozygous altered daughter cells. Both division systems showed co-segregating whole complements, which for reduction of the diploid metaphases could only arise from gonomeric-based autonomous behavior of maternal and paternal (mat/pat) genomes. The timely associated appearance with these latter divisions was fast growing small-cells (1/2 volume-size reduced from normal diploidy), which became homozygous from haploid, genomic doubling. Both reductive divisions thus produced genome altered progeny cells with GPA, which was associated with pre-cancer-like cell-phenotypic changes. Since both "undesirable" reductive divisions expressed orderly division sequences, their genetic controls were assumed to be "old genetics", evolutionarily conserved in the genome of man. Support for this idea was a search for evidential material in the evolutionary record from primeval time, when haploid organisms were established. The theory was that endopolyploid and gonomery-based reductive divisions relieved the early eukaryotic organisms from accidental, non-proliferative diploidy and polyploidy, bringing the organism back to vegetative haploid pro-liferation. Asexual cycles were common for maintenance of propagating haploid and diploid early unicellular eukaryotes. Reduction of accidental diploidy was referred to as "one-step meiosis" which meant gonomeric-based maternal and paternal genomic independent segregations. This interpretation was supported by exceptional chromosomal behaviors. However, multiple divisions expressing non-disjunction was the choice-explanation from evolutionists, which today is also suggested for the rarer LL-1 near haploid leukemia. These preserved non-mitotic mechanistic divisions systems are today witnessed in apomixes and parthenogenesis in many animal phyla. Thus, the indications are the modern genome of man harbors, relic-genetics from past "good" evolvements assuring "stable" proliferation of ancient, primitive eukaryotes, but with cancer-like effects for normal human cells.

The Cancer Aneuploidy Paradox: In the Light of Evolution

“…We saw that PM commonly occurs with a mitotically disabled spindle and closed telomeres, thereby evading practically all of the checkpoints of the mitotic cell cycle. Parental genome segregations with spindle un-coupling has been suggested by Walen in normal human senescing fibroblast cultures and in those treated with spindle poisons, and extrapolated to stem cell biology highlighting haploidy as an operating unit of genome segregations [93][94][95]. Such "exploded metaphases" [96] and segregation of haploid genomes [97] were reported previously.…”

Wound Healing Is a First Response in a Cancerous Pathway: Hyperplasia Developments to 4n Cell Cycling in Dysplasia Linked to Rb-Inactivation

“…Applicable to this in vivo question, is very likely, the in vitro well characterized genome reductive mechanistic division of tetraploid diplo-chromosomes, observed in pre-senescence associated with "genome damaged", short telomeres [17]- [22]. This irregular division, being meiotic-like, gave rise to only two types of progeny cells, 4n/4C/G1 and 2n/2C/G1, with the latter cells being pseudo-diploid with hyperplastic-like growth-morphology [13] [14]. For a construction of a sequence of cellular events in pre-neoplasia, these in vitro experimental data and cellular happenings in pre-neoplasia especially from ulcerative colitis and Barrett' esophagus (BE) were mainly considered.…”

“…This genome damage-associated hyperplasia was experimentally verified by experimental induction (virusvectors) of genomic damage with a resulting hyperplastic growth (GPA) from normal human cells. Genome damage (injured tissues) is one required precursor activity for activation of the evolutionary conserved "relic" DNA, which determines reductive mechanistic divisions [13] [14]. Interestingly, in the various proposals for a cancer initiating mechanism, there is little to no considerations of evolutionary conserved cellular phenomena.…”

“…An interesting suggestion has come from the fact that BE pre-neoplasia and matched adenocarcinoma shared pre-cursor molecular markers [79], a commentary suggested that "-genetic determinants of progression -" were "-preprogrammed from a very early stage in each potential cancer's life-" [80]. Is this idea in line with the discussed ontogenetic, evolutionary conserved "genetic" preprograming of the cancerous process [11]- [14]?…”

“…The present approach to the tumorigenic process also involved a concept of evolutionary conservation, which however, was arrived at from a genomic-behavioral analysis of primitive unicellular organisms when meiosis was non-existent [13] [14]. In the present review, it is accepted that development to "mature" pre-neoplasia with dysplastic lesions is pre-programed from evolutionary conserved primitive ways for maintenance of procreative-integrity.…”