Of the two different types of cancer-causing agents in cigarettes, one is derived from nicotine, and the other is called polycyclic aromatic hydrocarbons (PAHs).

Polycyclic aromatic hydrocarbons have been shown to cause DNA damage, leading to mutations in critical genes that cause cancer. Recently, researchers at the University of Pennsylvania’s School of Medicine have found that PAHs may also cause lung cancer through oxidative stress, which similarly leads to mutations in critical genes that cause the disease.

“This is a second, but indirect, way in which PAHs can cause cancer. We also know that PAHs can cause cancer directly,” says Ian Blair, PhD, co-author of the study.

The enzymes responsible for generating the oxidative stress from PAHs, called AKRs, are over expressed in lung cancer tumor tissue.

Through oxidative stress, the AKR enzymes transform PAHs to produce oxygen free radicals that can lead to cell death. The oxygen free radicals bind to DNA and, if left untreated, this damage can lead to mutations that are carried through to the next generation of cells.

“Because this study relates AKR over expression to oxidative damage of DNA with lung cancer, it makes you wonder if the 10% of smokers that are most prone to lung cancer have either dysregulated AKR expression or genetic differences in their AKRs that predispose them to the disease,” says Trevor Penning, PhD, senior author of the study.

“These findings go beyond the first step of DNA damage and may provide a reason why disease progresses,” says Penning.