Tobacco is a complex mixture of chemicals, some of which are toxic and/or carcinogenic. Animal studies designed to assess risk of tobacco smoke exposure have predominantly focused on either single chemical exposures or the more complex mixtures of tobacco smoke or its fractions. There are fewer studies investigating the interactions between specific tobacco smoke chemicals. Previous studies from our lab investigated the ability of inhaled formaldehyde or acetaldehyde to modify the pulmonary carcinogenic properties of NNK in A/J mice. These aldehydes significantly increased the number of lung adenomas with dysplasia and adenomas with progression without a significant enhancement of total lung adenomas. More recently, we tested the ability of a 3 h nose-only carbon dioxide (0, 5, 10 or 15%) co-exposure to influence lung adenoma formation by NNK (0, 2.5 or 7.5 µmol, i.p. in saline). Tobacco smoke contains 12.5% carbon dioxide and literature reports indicated that carbon dioxide inhalation can induce inflammation in the mouse lungs. While carbon dioxide alone did not increase lung adenomas in A/J mice, the co-exposure to carbon dioxide more than doubled the number of lung adenomas induced by 2.5 µmol NNK, with the maximal effect observed with 10% carbon dioxide (0%: 1.8 ± 1.9; 5%: 3.9 ± 2.8; 10%: 7.1 ± 3.5; 15%; 5.5 ± 2.9 lung adenomas/mouse). The co-exposure effect was less with 7.5 µmol NNK (0%: 11 ± 6.2; 5%: 13 ± 7.9; 10%: 18 ± 6.0; 15%; 12 ± 5.3 lung adenomas/mouse). These data indicate that carbon dioxide had a significant additive and synergistic effect on NNK-derived pulmonary adenomas (<i>p</i> value = 1.0 x 10<sup>-14</sup>). The mechanism of this interaction is under investigation. This study supports the hypothesis that the chemicals in tobacco smoke interact to form a more potent lung carcinogen.

Carbon dioxide enhances the pulmonary tumorigenic activity of the tobacco specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

2019 Fall National Meeting

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