Cotinine, and its parent compound nicotine, are highly specific for exposure to secondhand smoke. Because of its favourable biological half-life and the sensitivity of techniques for quantifying it, cotinine is currently the most suitable biomarker for assessing recent exposure to secondhand tobacco smoke uptake and metabolism in adults, children and newborns.
Several studies in humans have shown that concentrations of adducts of carcinogens to biological macromolecules, including haemoglobin adducts of aromatic amines and albumin adducts of polycyclic aromatic hydrocarbons, are higher in adult involuntary smokers and in the children of smoking mothers than in individuals not exposed to secondhand tobacco smoke. Protein adduct concentrations in fetal cord blood correlate with those in maternal blood but are lower. Fewer studies have investigated DNA adduct levels in white blood cells of exposed and unexposed nonsmokers, and most studies have not shown clear differences.
In studies of urinary biomarkers, metabolites of the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, have been found to be consistently elevated in involuntary smokers. Levels of these metabolites are 1–5% as great as those found in smokers. The data demonstrating uptake of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a lung carcinogen in rodents, by nonsmokers are supportive of a causal link between exposure to secondhand tobacco smoke and development of lung cancer.
The exposure of experimental animals, primarily rodents, to secondhand tobacco smoke has several biological effects that include (i) increases or decreases in the activity of phase I enzymes involved in carcinogen metabolism; (ii) increased expression of nitric oxide synthase, xanthine oxidase and various protein kinases; (iii) the formation of smoke-related DNA adducts in several tissues; and (iv) the presence of urinary biomarkers of exposure to tobacco smoke.
In adult experimental animals, sidestream tobacco smoke has been found to produce changes that are similar to those observed with exposure of humans to secondhand tobacco smoke. These include inflammatory changes in the airways and accelerated formation of arteriosclerotic plaques. Although the changes are often comparatively minor and require exposure to rather elevated concentrations of sidestream smoke, they support the results of human epidemiological studies. During pre- and postnatal exposure, sidestream smoke produces intrauterine growth retardation, changes the pattern of metabolic enzymes in the developing lung, and gives rise to hyperplasia of the pulmonary neuroendocrine cell population. In addition, it adversely affects pulmonary compliance and airway responsiveness to pharmacological challenges.
"In humans, involuntary smoking is associated with increased concentrations of mutagens in urine. Some studies have shown a correlation of urinary mutagenicity with concentrations of urinary cotinine. Increased levels of sister chromatid exchanges have not been observed in involuntary smokers; however, there is some indication of elevated levels in exposed children. Lung tumours from nonsmokers exposed to tobacco smoke contain TP53 and KRAS mutations that are similar to those found in tumours from smokers. The genotoxicity of sidestream smoke, ‘ environmental’ tobacco smoke, sidestream smoke condensate or a mixture of sidestream and mainstream smoke condensates has been demonstrated in experimental systems in vitro and in vivo.