Niacin requirements for genomic stability

Abstract

Through its involvement in over 400 NAD(P)-dependent reactions, niacin status has the potential to influence every area of metabolism. Niacin deficiency has been linked to genomic instability largely through impaired function of the poly ADP-ribose polymerase (PARP) family of enzymes. In various models, niacin deficiency has been found to cause impaired cell cycle arrest and apoptosis, delayed DNA excision repair, accumulation of single and double strand breaks, chromosomal breakage, telomere erosion and cancer development. Rat models suggest that most aspects of genomic instability are minimized by the recommended levels of niacin found in AIN-93 formulations; however, some beneficial responses do occur in the range from adequate up to pharmacological niacin intakes. Mouse models show a wide range of protection against UV-induced skin cancer well into pharmacological levels of niacin intake. It is currently a challenge to compare animal and human data to estimate the role of niacin status in the risk of genomic instability in human populations. It seems fairly certain that some portion of even affluent populations will benefit from niacin supplementation, and some subpopulations are likely well below an optimal intake of this vitamin. With exposure to stressors, like chemotherapy or excess sunlight, suraphysiological doses of niacin may be beneficial.

Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression

“…NIC and NAM are used to modulate NAD + levels and showed therapeutic effects in disorders, such as cerebral ischemia, diabetes, and cardiovascular dysfunctions (32,33). NIC and NAM protect neurons against oxidative damage, whereas subclinical vitamin B3 deficiency is associated with genomic instability and increased cancer risk (50).…”

“…We found that modulation of mTORC1 activity and autophagy by NAM involved SIRT1 activation in MDA-MB-453 cells, and likely depends on additional or alternative mechanisms in MDA-MB-435 and MDA-MB-231 cells. NAD + -dependent sirtuins and PARPs contribute to p53 function and regulate chromatin structure and genomic stability (32,33,50), thereby playing emerging roles in tumor progression (57). Moreover, the transcriptional corepressor CtBP responds to increased NADH under hypoxia to permit gene expression that promotes tumor cell migration (58).…”

Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis Evolved and Became a Determinant of Ageing Diseases: Hypotheses and Lessons from Pellagra

“…Sub pellagrous NAD deficiency may be a man-made socioeconomic “place” disease that rears its head episodically as a “time” disease triggering age-related infections, degenerations, and cancers [397]. This type of socioeconomic illness does not naturally trigger an empathetic response reducing the chances of resolving the situation [398].…”

Avaliação dos efeitos tóxicos resultantes da exposição crônica a baixas doses de chumbo e metilmercúrio, associados ou não, e do possível efeito protetor da niacina diante desta exposição

“…Na versão alcalina do teste, são detectadas lesões por quebras das fitas de DNA e sítios álcali lábeis (Singh et al, 1988 A capacidade de atuar na proteção a danos genotóxicos apresentada pela vitamina niacina já havia sido descrita anteriormente (Bartleman, Jacobs, & Kirkland, 2008;Kirkland, 2012). Em diferentes modelos experimentais, a deficiência de niacina tem sido relacionada a comprometimentos na parada do ciclo celular e apoptose, atraso no reparo do DNA por excisão, acúmulo de quebras das fitas de DNA, ruptura cromossomal, comprometimento do telômero e desenvolvimento de câncer (Kirkland, 2012). Por outro lado, a suplementação de niacina tem demonstrado proteção contra danos genotóxicos (Bartleman et al, 2008).…”

“…O NAD+ é o substrato para as enzimas PARP que catalisam a ligação da ADP-ribose a diversas proteínas cromossômicas. As proteínas poli-ADPribosiladas funcionam na replicação e reparo do DNA, bem como em vários processos celulares incluindo diferenciação e apoptose (Kirkland, 2012 Finalmente, a presença ou não de nutrientes com ação protetora aos efeitos da exposição ao mercúrio e ao chumbo pode responder, em parte, pelo motivo das diferenças observadas nos efeitos tóxicos em populações expostas a estes metais.…”