Mechanism Behind How Tobacco Carcinogens Cause Lung Cancer

by Rajshri on  May 30, 2008 at 3:11 PM Cancer News
RSS Email Print This Page Comment bookmark
Font : A-A+

 Mechanism Behind How Tobacco Carcinogens Cause Lung Cancer
Tobacco carcinogens cause lung cancer in an indirect way, researchers at the University of Pennsylvania's School of Medicine's Center of Excellence in Environmental Toxicology (CEET) have found

There are two types of cancer-causing agents in cigarettes-a nicotine-derived chemical and polycyclic aromatic hydrocarbons (PAHs).

Earlier studies have shown how PAHs damage DNA, with the emphasis on how PAHs bind directly to DNA itself, leading to the mutations in critical genes that cause disease.

Now, researchers have shown that PAHs, via oxidative stress, can also lead to mutations in critical genes important in lung cancer.

"This is the first demonstration of this link. This is a second, but indirect, way in which PAHs can cause cancer. We also know that PAHs can also cause cancer directly," said co-author Ian Blair, PhD, Professor and Vice Chair of the Department of Pharmacology.

Trevor Penning, PhD, CEET's director and the study's senior author, explained that several genetic studies have also shown that the enzymes responsible for generating the oxidative stress from PAHs are overexpressed in lung cancer tumour tissue and esophageal cancers.

"Our study also shows that those same enzymes, called AKRs, are responsible for the oxidative stress from PAHs in the human lung cells we used in our experiments," he added.

Oxidative stress is the accumulation of destructive molecules called free radicals that can lead to cell death. Free radicals damage cell membranes, proteins, or genetic material by 'oxidizing' them, the same way oxygen causes iron to rust.

The AKR enzymes transform PAHs to produce oxygen free radicals. These oxygen radicals bind to DNA, and if this damage is not repaired it leads to mutations that are carried through to the next generation of cells.

Penning also mentioned another genetic ramification due to this association.

A recent microarray study of all 30,000 human genes asked what genes were most over-expressed in non-small cell lung carcinoma.

Out of the eight genes that were most abundantly overexpressed, two were AKR enzymes.

"Because this study relates AKR overexpression to oxidative damage of DNA with lung cancer, it makes you wonder if the 10 percent of smokers that are most prone to lung cancer, have either dysregulated AKR expression or genetic differences in their AKRs that predispose them to disease," says Penning.

Because oxidative stress is also associated with tumour promotion, it is possible that his link may also explain other stages of the disease process.

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

The study is published online in the Proceedings of the National Academy of Sciences.

Source: ANI

Post a Comment

Comments should be on the topic and should not be abusive. The editorial team reserves the right to review and moderate the comments posted on the site.
Notify me when reply is posted
I agree to the terms and conditions

AKR1B10? It turns out to be something that's "rapidly reversible upon smoking cessation." [Reversible and permanent effects of tobacco smoke exposure on airway epithelial gene expression. Beane J, Sebastiani P, Liu G, Brody JS, Lenburg ME, Spira A.
Genome Biol. 2007;8(9]:R201.)

And who are Spira et al.? Why, they're the very same ones who cranked out the propaganda, which deceived the public to think that activation of the PI3K system, which is actually a sign of virus infection, is associated with smoking - by using the word "smokers" 76 times, while admitting at the bottom of (another) article that "this increased activity is independent of smoking status or other smoking-related disease." HPV is an example of an infection that's directly implicated in lung cancer.

Evidently Spira et al turned up their noses at AKR1B10, because unlike PI3K, it had no use for predicting lung cancer. There's even a study here that implicates DOWNregulation of AKR1B10 gene expression in colorectal cancer.

More News on:

Iodine Deficiency Disorder Lung Cancer Health Hazards of Smoking Smoking And Cancer Smoking And Tobacco Cancer and Homeopathy Cancer Facts Asbestosis Cancer Pneumoconiosis 

News A - Z


News Search

Medindia Newsletters

Subscribe to our Free Newsletters!

Terms & Conditions and Privacy Policy.

Find a Doctor

Stay Connected

  • Available on the Android Market
  • Available on the App Store

News Category

News Archive