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

Nicotinamide is a water-soluble amide form of niacin (nicotinic acid or vitamin B3). Both niacin and nicotinamide are widely available in plant and animal foods, and niacin can also be endogenously synthesized in the liver from dietary tryptophan. Nicotinamide is also commercially available in vitamin supplements and in a range of cosmetic, hair, and skin preparations. Nicotinamide is the primary precursor of nicotinamide adenine dinucleotide (NAD+), an essential coenzyme in ATP production and the sole substrate of the nuclear enzyme poly-ADP-ribose polymerase-1 (PARP-1). Numerous in vitro and in vivo studies have clearly shown that PARP-1 and NAD+ status influence cellular responses to genotoxicity which can lead to mutagenesis and cancer formation. This paper will examine the role of nicotinamide in the protection from carcinogenesis, DNA repair, and maintenance of genomic stability

A UVB Wavelength Dependency for Local Suppression of Recall Immunity in Humans Demonstrates a Peak at 300nm

UVB radiation is a potent environmental carcinogen that not only causes mutations in the skin but also profoundly suppresses skin immune responses. Although this UVB-induced suppression of antitumor immunity has a key role in skin cancer development, the wavelengths within UVB causing greatest in vivo immunosuppression in humans are as yet unknown. We have identified a wavelength dependency for immunosuppression in humans across the UVB spectrum. We established linear dose–response curves for UV-induced local suppression of recall contact hypersensitivity responses at four wavelengths between 289 and 322nm and found peak immune suppressive effectiveness at 300nm and no detectable suppression at 322nm within a physiologically relevant dose range

IMPLEMENTASI PROGRAM KURIKULUM TINGKAT SATUAN PENDIDIKAN DI DAERAH STUDI KASUS SMP 2 NGRAMBE KECAMATAN NGRAMBE KABUPATEN NGAWI JAWA TIMUR

Education is one of the human rights of the most fundamental. An obligation for the state to build a community education in the context of national life, as stated in the 1945 Constitution, paragraph 4. Implementation of regional autonomy led to the decentralization of education in an effort to boost the development of education, then the school year 2006/2007 the government began to implement unit level education curriculum (SBC) that provides the broadest authority for schools to make their own curriculum in accordance with the ability to be able to bring seeds later in the day. Implementation of the policy is defined as any action in order to achieve policy goals and objectives that have been formulated while the curriculum is a set of plans and arrangements regarding the purpose, content, and teaching materials and methods used to guide the implementation of learning activities to achieve specific educationalgoals. The data analysis technique used in this study is an interactive analysis technique is a qualitative data analysis technique that consists of three flow activities, namely (1) data reduction, (2) the presentation of the data, and (3) concluding that occur simultaneously (Milen and Huberman, 1992: 16). Results of this study indicate that in implementing the curriculum or the Education Unit at SMP Negeri 2 Ngrambe not optimal because there are still problems such as lack of social

Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin.

Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV) radiation and affects DNA damage and repair. Nicotinamide (vitamin B3) reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2) solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer

Nicotinamide reduced arsenic and UV-induced 8oxoG levels in the epidermal layer of <i>ex vivo</i> human skin at 45 minutes after UV irradiation (a).

<p>Samples were exposed to either 50μM nicotinamide, 2μM sodium arsenite, PBS (control) with or without 2J/cm² of UV. The columns represent the mean ±SEM (n = 3). * = p<0.05, ** = p<0.01 one way ANOVA. <b>Staining of 8oxoG 45 minutes following UV radiation, arsenic and nicotinamide exposure in <i>ex-vivo</i> human skin (b)</b>. The blue staining represents DAPI (nuclear staining). The red staining represents 8oxoG staining.</p

Nicotinamide (NAM) reduced arsenic- (As) and UV-induced 8oxoG in HaCaT keratinocytes (a).

<p>HaCaT keratinocytes were exposed to either 50μM nicotinamide, 2μM sodium arsenite, both sodium arsenite and nicotinamide or PBS (control) alone, with or without UV. Grey lines represent unirradiated groups. The mean of each timepoint is displayed ± SEM (n = 3). Significant differences included UV versus (vs) no UV (p<0.05), UV vs UV + As (p<0.01), UV vs UV + NAM (p<0.05) and UV + As vs UV + As + NAM (p<0.05) two way ANOVA. <b>Staining of 8oxoG 45 minutes following UV radiation and arsenic exposure in HaCaT keratinocytes (and in unirradiated keratinocytes) shows reduced 8oxoG in irradiated, nicotinamide treated cells (b)</b>. The blue staining represents DAPI (nuclear staining). The red staining represents 8oxoG staining.</p

HaCaT human keratinocytes or ex vivo human skin samples were incubated ± 50μM nicotinamide (NAM) for 24h, and then incubated ± NAM and ± 2μM sodium arsenite (As) for a further 24h.

<p>Samples were then irradiated with a single, fixed dose of solar-simulated UV (2J/cm²), before once again being incubated ±NAM and ±As as per their pre-irradiation treatment allocation. The HaCaT cells were allowed to incubate for various periods before fixation; 15, 30, 45 and 75 minutes for oxidative DNA damage and 15, 45, 75 and 120 minutes for cyclobutane pyrimidine dimers. Skin samples were incubated for 45 minutes post-irradiation, when peak levels of DNA photolesions were observed.</p

Viability of HaCaT keratinocytes is not affected by exposure to nicotinamide (NAM), sodium arsenite (As) and UV.

<p>HaCaT keratinocytes were exposed to 50μM nicotinamide, 2μM sodium arsenite or PBS (control) alone, with and without irradiation with 2 J/cm² of UV. Columns represent the mean of the experiments ±SEM (n = 6). There were no significant differences detected between the groups p>0.05, one way ANOVA.</p

Nicotinamide (NAM) reduced arsenic (As) and UV-induced CPDs in HaCaT keratinocytes over time (a).

<p>The cells were stained for CPDs with grey lines representing unirradiated groups. The mean of each timepoint is displayed ± SEM (n = 3). Significant differences included UV vs no UV (p<0.01), UV vs UV + NAM (p<0.05) and UV + As vs UV + As + NAM (p<0.05) two way ANOVA. <b>Staining of CPDs 45 minutes following UV radiation, arsenic and nicotinamide exposure in HaCaT keratinocytes and in unirradiated keratinocytes (b)</b>. The blue staining represents DAPI (nuclear staining). The red staining represents CPD staining.</p

Nicotinamide reduced UV-induced CPDs in arsenic-treated and control irradiated <i>ex vivo</i> human skin at 45 minutes after UV irradiation (a).

<p>Samples were exposed to either 50μM nicotinamide, 2μM sodium arsenite, PBS (control) with or without 2J/cm² of UV. The columns represent the mean ±SEM (n = 3). * = p<0.05, ** = p<0.01 one way ANOVA. <b>Staining of CPDs 45 minutes following UV radiation and arsenic exposure in <i>ex-vivo</i> human skin (b)</b>. The blue staining represents DAPI (nuclear staining). The red staining represents CPD staining.</p