Targeting of Lung Cancer Mutational Hotspots by Polycyclic Aromatic Hydrocarbons

Leslie E. Smith, Mikhail F, Denissenko, William P, Bennett, et al
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2001

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Reviewers: Li Liu, MD
Source: Journal of the National Cancer Institute volume 92, 803-811 (May) 2000

Introduction

Gasoline and diesel engines and other industrial sources release chemicals called polycyclic aromatic hydrocarbons (PAH's) into the environment. The largest source of PAH's, however, is cigarette smoke. PAH's have been associated with lung cancer since these compounds can lead to mutations in the p53 tumor suppressor gene, which are present in about 60% of all lung cancer cases. In this study, the researchers mapped the genetic changes in normal human bronchial epithelial cells induced by PAHs' metabolites.

Materials and Methods

  • Normal human bronchial epithelial cells were exposed to PAH's and DNA mutations of p53 genes were subsequently analyzed.
  • The researchers compared the changes to a database of p53 mutations that occur in lung cancer.

Results

  • The distribution of the location of the damage matched well with the mutations in lung cancer.
  • The sites most often damaged by PAHs were the sites of the most common mutations in lung cancer.

Discussion

In this study, a class of chemicals formed as tobacco burns led to genetic changes that are often seen in human lung cancer. This study provided important additional support for the critical role of metabolically activated carcinogens in the induction of human lung cancer. Avoiding exposure to these compounds is a key to decreasing lung cancer incidence.



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