Niacin deficiency modulates genes involved in cancer: Are smokers at higher risk?

Abstract

The role of niacin's metabolite, nicotinamide adenine dinucleotide (NAD), in DNA repair via base-excision repair pathway is well documented. We evaluated if niacin deficiency results in genetic instability in normal human fetal lung fibroblasts (MRC-5), and further, does it leads to enhanced accumulation of cigarette smoke-induced genetic damage? MRC-5 cells were grown discretely in niacin-proficient/deficient media, and exposed to nicotine-derived nitrosamine ketone (NNK, a cigarette smoke carcinogen). Niacin deficiency abated the NAD polymerization, augmented the spontaneous induction of micronuclei (MN) and chromosomal aberrations (CA) and raised the expression of 10 genes and suppressed 12 genes involved in different biological functions. NNK exposure resulted in genetic damage as measured by the induction of MN and CA in cells grown in niacin-proficient medium, but the damage became practically marked when niacin-deficient cells were exposed to NNK. NNK exposure raised the expression of 16 genes and suppressed the expression of 56 genes in cells grown in niacin-proficient medium. NNK exposure to niacin-deficient cells raised the expression of eight genes including genes crucial in promoting cancer such as FGFR3 and DUSP1 and suppressed the expression of 33 genes, including genes crucial in preventing the onset and progression of cancer like RASSF2, JUP, and IL24, in comparison with the cells grown in niacin-proficient medium. Overall, niacin deficiency interferes with the DNA damage repair process induced by chemical carcinogens like NNK, and niacin-deficient population are at the higher risk of genetic instability caused by cigarette smoke carcinogen NNK.

B Vitamins and Their Role in Immune Regulation and Cancer

“…NAD is also involved in the maintenance of genomic stability and regulation of enzymes involved in epigenetic regulation [49]. NAD-dependent enzymes are involved in base excision repair [50]. High NAD levels (NAD/NADH) inhibit ROS production [51].…”

Hepatic transcript profiling in beef cattle: Effects of rumen-protected niacin supplementation

“…As for the other significant pathways involved in cellular processes, it is worth mentioning the downregulation of cell motility and cell community KEGG categories, which mainly rely on the downregulation of the “regulation of actin cytoskeleton” pathway and “focal adhesion” pathway. A recent article investigating niacin deficiency and genetic instability also reported alterations of the focal adhesion signaling pathway in niacin-deficient cells in humans [ 42 ]. Focal adhesions are involved in various cellular processes, including migration, proliferation, and differentiation [ 43 ].…”

The 4 D’s of Pellagra and Progress

“…174,175 Similarly, with cancer, autoimmune and metabolic syndromes, there is biochemical evidence of loss of nicotinamide homeostasis, whether dietary from increased consumption or excessive catabolism, or implied from benefits of measurement and intervention. 153,176-203…”