Sporotrichosis in cats from southeast Brazil

Abstract

Background: N'-Nitrosonornicotine (NNN) and acetaldehyde are major constituents of tobacco smoke. NNN acts as a potent oral carcinogen by forming pyridyloxobutyl DNA adducts following metabolic activation. Acetaldehyde is a strong electrophile and acts as a direct genotoxicant, inducing DNA adducts and cross-links and inhibiting DNA repair. Since tobacco smoke is a complex mixture of toxic and carcinogenic chemicals, studying the interaction of specific tobacco chemicals increases the relevance of toxicologic studies to understanding health risks associated with smoking tobacco. Objective: To investigate whether acetaldehyde potentiates the carcinogenic effect of NNN with respect to tumorigenesis. Methods: Nine groups of male F344 rats (n=15) were exposed in the drinking water to 0, 4 or 8 ppm NNN for up to 100 weeks in the presence or absence of 3000 ppm acetaldehyde. Oral and esophageal lesions in animals surviving beyond 69 weeks were classified as atypical epithelial hyperplasia (AEH) or squamous papilloma (SP). Results: NNN dose-dependently significantly increased the number of animals with AEH (n=6 of 10 vs n=3 of 12 animals) and the number of SP (n=9 vs n=2), typically involving esophagus, for the 8 and 4 pm groups, respectively. Acetaldehyde alone was not tumorigenic, but significantly increased the number of NNN-exposed rats exhibiting AEH (n=13 of 13 and n=7 of 12 animals, 8 vs 4 ppm groups respectively), and significantly increased the number of SP in the 8 ppm group (n=20) although not the 4 ppm group (n=2). Conclusions: Acetaldehyde potentiates the oncogenesis of N'-nitrosonornicotine in F344 rats.