Tobacco
smoke is a
complex mixture of chemicals, many of which are toxic and carcinogenic. Hazard assessments 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 exploring interactions between specific tobacco
smoke chemicals.
Aldehydes such as
formaldehyde and
acetaldehyde were hypothesized to enhance the carcinogenic properties of the human
carcinogen, 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) through a variety of mechanisms. This hypothesis was tested in the established NNK-induced A/J mouse lung
tumor model. A/J mice were exposed to NNK (
intraperitoneal injection, 0, 2.5, or 7.5 μmol in saline) in the presence or absence of
acetaldehyde (0 or 360 ppmv) or
formaldehyde (0 or 17 ppmv) for 3 h in a nose-only inhalation chamber, and lung
tumors were counted 16 weeks later. Neither
aldehyde by itself induced lung
tumors. However, mice receiving both NNK and
acetaldehyde or
formaldehyde had more
adenomas with dysplasia or progression than those receiving only NNK, suggesting that
aldehydes may increase the severity of NNK-induced lung
adenomas. The
aldehyde coexposure did not affect the levels of NNK-derived
DNA adduct levels. Similar studies tested the ability of a 3 h nose-only
carbon dioxide (0, 5, 10, or 15%) coexposure to influence lung
adenoma formation by NNK. While
carbon dioxide alone was not carcinogenic, it significantly increased the number of NNK-derived lung
adenomas without affecting NNK-derived DNA damage. These studies indicate that the chemicals in tobacco
smoke work together to form a potent lung carcinogenic mixture.