Tobacco Xenobiotics Release Nitric Oxide

Many xenobiotic compounds exert their actions through the release of free radicals and related oxidants 12, bringing about unwanted biological effects 3. Indeed, oxidative events may play a significant role in tobacco toxicity from cigarette smoke. Here, we demonstrate the direct in vitro release of the free radical nitric oxide (*NO) from extracts and components of smokeless tobacco, including nicotine, nitrosonornicotine (NNN) and 4-(methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in phosphate buffered saline and human saliva using electron spin resonance and chemiluminescence detection. Our findings suggest that tobacco xenobiotics represent as yet unrecognized sources of *NO in the body.