Inflammation and Carcinogenesis Are Enhanced in a Modified 4-Nitroquinolone 1-Oxide and Ethanol Animal Model

Abstract

Chemical carcinogen 4-NQO is widely used in animal studies for induction of squamous carcinoma (SCC) in the upper aerodigestive tract (UADT), as it mimics the effects of smoking tobacco. Typical murine protocols deliver 4-NQO in drinking water alone for several weeks, followed by weeks of observation, with or without addition of ethanol during the follow-up. Important drawbacks of these methods are the long time to generation of tumors (25-35 weeks), as well as sparse mucosal inflammation. Moreover, recent studies indicate that inflammatory pathways regulated by microbial toll-like receptor 2 (TLR2) may contribute to carcinogenesis at mucosal surfaces.