Role of Nicotinamide in DNA Damage, Mutagenesis, and DNA Repair

Conclusion:

Nicotinamide, which is the dietary precursor for NAD+, provides a substrate for PARP-1 activity…. In various murine models, PARP-1 inhibition was shown to favor apoptotic cell death, reduce inflammatory response, and reduce genomic sensitivity to various carcinogens. However, extrapolation of these data to human, particularly when physiological regimes involved in human carcinogenesis, should be done cautiously. Further studies are needed to determine the effect of high-dose nicotinamide on in vivo carcinogenesis and genomic stability of the cancer cells and the surrounding normal cells.

My comment: The likelihood that vitamin B3 has similar nutrient-dependent effects in humans is addressed in:

Study: Vitamin B3 May Help Prevent Certain Skin Cancers

Excerpt:

The study involved 386 people who had at least two skin cancers in the previous five years. They took either 500 milligrams of the vitamin or dummy pills twice a day for a year.

My comment: Those who took B3 developed fewer than two of these cancers on average compared to ~2.5 cancers for the others.

The difference this could make to me could have been ~2.2 fewer cancers per year (18 vs 20). If even one of those two was another malignant melanoma, it probably would be worth the cost of the supplement.

The cost of the supplement could also be viewed in the context of nutrient-dependent RNA-directed DNA methylation and RNA-mediated cell type differentiation via amino acid substitutions. For example, the light-induced de novo creation of amino acids (see: On the Origins of Life) links nutritional epigenetics to what is currently known about the biophysically constrained chemistry of RNA-mediated protein folding in all genera.

Nutrient-dependent amino acid substitutions differentiate the cell types of all cells in all individuals of all genera. That is how RNA-mediated amino acid substitutions are linked to biodiversity. The fixation of amino acid substitutions occurs via the physiology of nutrient-dependent reproduction.

RNA-mediated cell type differentiation via amino acid substitutions helps to explain why mutations, which perturb protein folding, cannot be linked to evolution and biodiversity. Instead, perturbed protein folding is linked to pathology, like skin cancers.

This claim was made in the 2013 textbook Mutation-Driven Evolution

Conclusion:

“In other words, genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world. In this view of evolution there is no need of considering teleological elements” (p. 199).

Nei likes the ideas of the population geneticists who invented neo-Darwinism based on de Vries definition of “mutation” and their assumptions about how long it might take for one species to evolve into another species, which is not possible. See for comparison, my invited review of nutritional epigenetics: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

Abstract excerpt:

Ideas from population genetics, which exclude ecological factors, are integrated with an experimental evidence-based approach that establishes what is currently known. This is known: Olfactory/pheromonal input links food odors and social odors from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man during their development.

My comment: My ideas include links from ecological variation to ecological adaptations in all genera. For example, I linked the light-induced de novo creation of amino acids to the RNA-mediated amino acid substitutions that differentiate all the cell types of all individuals of all genera. My ideas also were included in several of the articles that were published in a special issue of “Nutrients.” (The editors of the special issue requested my review, but supposedly no one would review my review.)

However, conveying my ideas is what’s most important to me. See for example: The Interaction between Epigenetics, Nutrition and the Development of Cancer

Abstract excerpt:

These “later life” epigenetic modifications in response to dietary intervention are the focus of this paper. The epigenetic modifications investigated include DNA methylation, histone modifications and the influence of microRNAs.

From my invited review: 

In Section One, the focus is on links between atoms and ecosystems via amino acid substitutions. In Section Two, the focus is on examples of links across a continuum of nutrient-dependent, pheromone-controlled, epigenetically-effected, receptor-mediated ecological adaptations via amino acid substitutions and changes in the microRNA/messenger RNA balance.

Without the integration of my ideas in a cohesive review, many researchers might get the impression that claims of  Mutation-Driven Evolution are supported by experimental evidence of biologically-based cause and effect. Nothing could be further from the truth. That’s why many serious scientists are Combating Evolution to Fight Disease.

The truth is: “Let there be light” in the context of Biblical Genesis is linked to The Miracles Of Smell And Taste via the experience-dependent de novo creation of olfactory receptor genes in vertebrates and invertebrates. The creation of the new genes links the nutrient-dependent pheromone-controlled physiology of reproduction in species from microbes to man via the conserved molecular mechanisms of biophysically constrained protein folding during life history transitions. Simply put, I detailed what is currently known about epigenetic links between metabolic networks and genetic networks without including any of the pseudoscientific nonsense about mutations and evolution.

Obviously, the focus of serious scientists has changed to what is known about RNA-mediated DNA repair mechanisms and ecological adaptations manifested in the morphological and behavioral phenotypes of all genera.   The role played by vitamin B3 is another example of how the focus has changed from mutations that perturb protein folding and cause pathology, to nutrient-dependent DNA repair and transgenerational epigenetic effects on health and longevity. Simply put, the focus has changed from ridiculous theories to facts about the creation of different cell types via what is currently known about physics, chemistry, and molecular biology.  See for example: Clinically Actionable Genotypes Among 10,000 Patients With Preemptive Pharmacogenomic Testing

Pharmacogenomic testing links what is known about nutritional epigenetics to cell type differentiation via theromodynamic cycles of protein biosynthesis and degradation that are perturbed by mutations. Obviously, what is known about cell type differentiation links mutations to pathology, not to evolution. It also links the sun’s biological energy to the creation of cells and cell types in all genera via the physiology of nutrient-dependent reproduction.

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