Prevention of photoimmunosuppression and photocarcinogenesis by topical nicotinamide

Abstract

Ultraviolet (UV) B irradiation leads to a potent immunosuppression of the capacity to reject syngeneic, antigenic tumors. If this immunosuppression is critical for the development of most skin tumors, then its prevention should result in prevention of photocarcinogenesis. We previously showed a correlation between the inhibition of photoimmunosuppression and prevention of photocarcinogenesis by dl-alpha-tocopherol, tannic acid, or alpha-difluoromethylornithine. The current study was designed to determine whether topical nicotinamide, the active form of vitamin B-3, or niacin, prevents immunosuppression and skin cancer in UV-irradiated mice. In a passive transfer assay for immunosuppression, splenocytes from UV-irradiated mice enhanced the growth of antigenic tumor challenges in recipient mice. Treatment of the UV-irradiated mice with 40 mumol of nicotinamide twice weekly starting two weeks before UV irradiation and throughout the experiment prevented this immunosuppression. UVB irradiation consisted of five weekly 30-minute exposures to banks of six FS40 Westinghouse fluorescent sunlamps. Mice received approximately 6.2 x 10(5) J/m2 in the passive transfer assays and 1.09 x 10(6) J/m2 in the photocarcinogenesis studies. Application of nicotinamide to UV-irradiated mice reduced skin tumor incidence from 75% to 42.5% (p = 0.016, Cox proportional hazards analysis). Thus topical nicotinamide prevented the immunosuppression and skin tumor induction by UVB irradiation.

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

“…In mice, 200  μ M topical nicotinamide [52] and 0.5% and 1% niacin-supplemented diets [53] have both been shown to markedly protect against UV-induced immunosuppression and significantly reduce the incidence of UV-induced skin tumours. In these studies, UV-induced immunosuppression was measured by passive transfer assay, whereby splenocytes from irradiated mice enhanced the growth of antigenic tumours in unirradiated, recipient mice [52, 53].…”

New Dimeric Copper(II) Complex [Cu(5‐MeOsal)2(μ‐nia)(H2O)]2 with Magnetic Exchange Interactions through H‐Bonds

“…Nicotinamide (also known as a niacin derivative or vitamin B 3 ) is a nitrogen donor ligand that has been used in the treatment of various skin diseases (atopic eczema, [1,2] psoriasis and skin cancer [3][4][5] ), and the biological activity of its copper complexes have also been studied. [6] In addition, the biological activity of different salicylic acid derivatives and their copper(II) complexes is well known.…”

Niacinamide - Mechanisms of Action and Its Topical Use in Dermatology

“…Moloney et al [71] investigated the effectiveness of a 1% niacinamide preparation versus vehicle regarding the number of actinic keratoses over 6 months and could not find relevant differences. In studies with recall antigen tests Gensler [72] could prove in vivo that niacinamide reduces UV-induced immunosuppression. Further studies of photocarcinogenesis and photoprotection do not exist.…”