Exposure to polycyclic aromatic hydrocarbons may increase cancer risk

California NanoSystems InstituteOct 28 2024

Derek Urwin has a special stake in his work as a cancer control researcher. After undergraduate studies in applied mathematics at UCLA, he became a firefighter. His inspiration to launch a second career as a scientist was the loss of his brother, Isaac, who died of leukemia at only 33 despite no history of cancer in their family. Working with Anastassia Alexandrova, a professor of chemistry and biochemistry in the UCLA College, he earned his doctorate.

Urwin is now a UCLA adjunct professor of chemistry -; and still a full-time firefighter with the Los Angeles County Fire Department. In a recent publication, his science shed new light on the chemical underpinnings of exposures that may lead to cancer.

When organic substances burn, the smoke carries compounds known as polycyclic aromatic hydrocarbons, or PAHs. PAHs can enter the body through breathing, eating, drinking and skin contact. Because emissions from industry and automobiles are one source, nearly everyone encounters these chemicals in day-to-day life. Certain jobs such as firefighting and coal-tar production expose workers to concentrated doses of PAHs -; the same jobs that tend to be associated with increased risk for cancer.

In fact, the International Agency for Research on Cancer has listed many PAHs as probable or possible carcinogens. Only one among these thousands of chemicals, benzo[a]pyrene (B[a]P), is classified as a known carcinogen in humans.

A study by Urwin, Alexandrova and UCLA undergraduate Elise Tran published in the Proceedings of the National Academy of Sciences shows that some of B[a]P's chemical cousins may present more serious risk for cancer. The scientists used computer simulations of molecular interactions to profile what happens when each of 15 PAHs settles onto a spot in the DNA helix commonly linked to cancer-causing mutations. Compared to the known carcinogen, six of the PAHs showed a greater affinity for binding to the mutational hotspot. Those six chemicals also had a higher likelihood of avoiding detection by a crucial mechanism for repairing DNA lesions.

At left is a molecule that is a known carcinogen, and at right a chemical cousin. The green dashes surround an extra space that might connect to DNA; that space is obscured inside the orange dashes.

In addition to the new insight about the relative toxicity of PAHs, the research may offer a faster way to filter potentially dangerous chemicals and identify which ones are riskiest to human health. Such findings could inform not only laboratory and population studies but also public policy.

We hope that our strategy can speed up the process of studying these chemicals. Instead of casting a wide net, this could show exactly where we ought to start the process. Efficient, effective, accurate computational studies can even enhance or accelerate the process of developing policy that improves public and occupational health."

Derek Urwin, study's first author

Urwin also serves as chief science advisor for the International Association of Fire Fighters and was recently appointed to the California Occupational Safety and Health Standards Board.

"Derek's work as a firefighter made this research possible," said corresponding author Alexandrova, who is a member of the California NanoSystems Institute at UCLA. "He knows what's going on in the field very intimately, and that enables us to make the connection to chemistry and the tools that we have. Real-life experience educated us about what to do."

Credit is also due to Urwin's intuition. The germ of the investigation was his observation that, based on their structure, several PAHs simply looked as though they ought to fit more snugly within the DNA double helix than others, where they insert themselves like a key into a keyhole.

The investigators built on previous research in which they applied an advanced algebraic technique to accurately model PAHs' atomic interactions. They compared how strongly B[a]P and 14 other PAHs bind to a DNA sequence that is mutated in one third of all human cancers.

The team plans to apply their computational method to other genetic hot spots related to cancer, as well as to more PAHs and other compounds, including the "forever chemicals" known as PFAS.

With connections to the world of firefighting and science, Urwin also relishes the opportunity for community-based participatory research. In that model, the people being studied help shape the questions being asked, the design and execution of the research, and the dissemination of resulting information to those affected in a way that they understand.

"My fellow firefighters have historically been underserved by the scientific community, not out of disdain, but rather because it's complicated to conduct research in the midst of emergency service operations," Urwin said. "Having my feet in both arenas, I want to bring access to scientists, so their research can create a positive impact on health in the fire service community. Science is supposed to make the world better for people, whether it's firefighters or anyone else."