Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice

Topical nicotinamide (niacinamide) has demonstrable preventive activity aga inst photocarcinogenesis in mice. To better understand how this vitamin pre vents ultraviolet (UV) carcinogenesis, we tested systemic administration of another form of the vitamin, niacin, and its capacity to elevate cutaneous nicotinamide-adenine dinucleotide (NAD) content as well as to decrease pho toimmunosuppression and photocarcinogenesis. BALB/cAnNTacfBR mice were fed the AIN-76A diet supplemented with 0% 0.1%, 0.5%, or 1.0% niacin throughout the experiment. UV irradiation consisted of five 30-minute exposures per w eek to banks of six FS40 Westinghouse sunlamps for 22 week in the carcinoge nesis experiments, yielding a total cumulative dose of approximately 1.41 x 10(6) Jm(-2) of UV-B radiation. Dietary supplementation with 0.1%, 0.5%, o r 1.0% niacin reduced the control incidence of skin cancer from 68% to 60%, 48%, and 28%, respectively, at 26.5 week after the first UV treatment TWO potential mechanisms by which niacin prevents tumor formation were identifi ed. Photoimmunosuppression, critical for photocarcinogenesis, is measured b y a passive transfer assay. Syngeneic, antigenic tumor challenges grew to a n average of 91.6 +/- 19.7 79.8 +/- 11.5, 41.9 +/- 11.7, or 13.2 +/- 4.1 mm (2) in naive recipients of splenocytes from UV-irradiated mice treated with 0%, 0.1%, 0.5%, or 1.0% niacin supplementation, respectively, demonstratin g niacin prevention of immunosuppression. Niacin supplementation elevated s kin NAD content, which is known to modulate the function of DNA strand scis sion surveillance proteins p53 and poly(ADP-ribose) polymerase, two protein s critical in cellular responses to UV-induced DNA damage. These results cl early demonstrate a dose-dependent preventive effect of oral niacin on phot ocarcinogenesis and photoimmunosuppression and establish the capacity of or al niacin to elevate skin NAD levels.