Nicotinamide, the amide form of vitamin B3, and budesonide, a synthetic glucocorticoid used in the treatment of asthma, were evaluated for efficacy of chemoprevention of lung adenoma formation in a benzo(a)pyrene murine carcinogenesis model. Female A/J mice were given three doses of 3 mg benzo[a]pyrene three days apart and started on experimental diets either 1 week (early stage intervention) or 8 weeks (late stage) after last carcinogen dose. Aerosol treatments were delivered 5 days per week starting 1 or 8 weeks post carcinogen. Nicotinamide, fed at a dietary concentration of 0.75% starting 1 week after last carcinogen administration, inhibited adenoma formation by 54%, and by 39% when begun 8 weeks post final carcinogen. Nicotinamide fed at 0.25% of the diet was not found to effect adenoma formation . Dietary nicotinamide under the same conditions with budesonide administered via aerosol administration at 25μg/kg, reduced lung adenoma formation by 90% at early stage intervention and 49% at late stage intervention. Budesonide alone administered at the same dose level gave 77% inhibition at early stage and 41% inhibition at late stage. Decreases in adenoma formation were statistically significant via ANOVA analysis at both early and late interventions. Combination therapy decreased adenoma formation significantly over either individual therapy at the early stage and significantly compared to nicotinamide alone at the late stage. However, administration of nicotinamide by aerosol inhalation at doses up to 15 mg/kg/day did not result in a statistically significant reduction in tumor multiplicity at 1 or 8 weeks post last carcinogen administration . There is a high level of clinical interest in minimal toxicity lung cancer chemoprevention strategies. We feel administration of a safe dietary agent such as nicotinamide when combined with direct epithelial delivery of a glucocorticoid such as budesonide, commonly used for asthma therapy, is a promising approach for aerodigestive chemoprevention.
Citation Format: Donna Seabloom, Beverly Wuertz, Art Galbraith, Jenny Antonides, Vernon Steele, Lee Wattenberg, Frank G. Ondrey. Chemoprevention of lung carcinogenesis by dietary nicotinamide and inhaled budesonide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5267. doi:10.1158/1538-7445.AM2017-5267