Nav: Home

New clues about the risk of cancer from low-dose radiation

March 10, 2015

Scientists from the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) have uncovered new clues about the risk of cancer from low-dose radiation, which in this research they define as equivalent to 100 millisieverts or roughly the dose received from ten full-body CT scans.

They studied mice and found their risk of mammary cancer from low-dose radiation depends a great deal on their genetic makeup. They also learned key details about how genes and the cells immediately surrounding a tumor (also called the tumor microenvironment) affect cancer risk.

In mice that are susceptible to mammary cancer from low-dose radiation, the scientists identified more than a dozen regions in their genomes that contribute to an individual's sensitivity to low-dose radiation. These genome-environment interactions only become significantly pronounced when the mouse is challenged by low-dose radiation.

The interactions also have a big impact at the cellular level. They change how the tumor microenvironment responds to cancer. Some of these changes can increase the risk of cancer development, the scientists found.

They report their research in the March 9 issue of the journal Scientific Reports.

Because mice and humans share many genes, the research could shed light on the effects of low-dose radiation on people. The current model for predicting cancer risk from ionizing radiation holds that risk is directly proportional to dose. But there's a growing understanding that this linear relationship may not be appropriate at lower doses, since both beneficial and detrimental effects have been reported.

"Our research reinforces this view. We found that cancer susceptibility is related to the complex interplay between exposure to low-dose radiation, an individual mouse's genes, and their tumor microenvironment," says Jian-Hua Mao of Berkeley Lab's Life Sciences Division.

Mao led the research in close collaboration with fellow Life Science Division researchers Gary Karpen, Eleanor Blakely, Mina Bissell, and Antoine Snijders, and Mary Helen Barcellos-Hoff of New York University School of Medicine.

The identification of these genetic risk factors could help scientists determine whether some people have a higher cancer risk after exposure to low-dose radiation. It could lead to genetic screening tests that identify people who may be better served by non-radiation therapies and imaging methods.

The scientists used a comprehensive systems biology approach to explore the relationship between genes, low-dose radiation, and cancer. To start, Mao and colleagues developed a genetically diverse mouse population that mimics the diversity of people. They crossed a mouse strain that is highly resistant to cancer with a strain that is highly susceptible. This yielded 350 genetically unique mice. Some were resistant to cancer, some were susceptible, and many were in between.

Next, Mao and colleagues developed a way to study how genes and the tumor microenvironment influence cancer development. They removed epithelial cells from the fourth mammary gland of each mouse, leaving behind the stromal tissue. Half of the mice were then exposed to a single, whole-body, low dose of radiation. They then implanted genetically identical epithelial cells, which were prone to cancer, into the fourth mammary glands that were previously cleared of their epithelial cells.

"We have genetically different mice, but we implanted the same epithelial cells into all of them," says Mao. "This enabled us to study how genes and the tumor microenvironment--not the tumor itself--affect tumor growth."

The scientists then tracked each mouse for 18 months. They monitored their tumor development, the function of their immune systems, and the production of cell-signaling proteins called cytokines. The researchers also removed cancerous tissue and examined it under a microscope.

They found that low-dose radiation didn't change the risk of cancer in most mice. A small minority of mice was actually protected from cancer development by low-dose radiation. And a small minority became more susceptible.

In this latter group, they found thirteen gene-environment interactions, also called "genetic loci," which contribute to the tumor susceptibility when the mouse is exposed to low-dose radiation. How exactly these genetic loci affect the tumor microenvironment and cancer development is not yet entirely understood.

"In mice that were susceptible to cancer, we found that their genes strongly regulate the contribution of the tumor microenvironment to cancer development following exposure to low-dose radiation," says Mao.

"If we can identify similar genetic loci in people, and if we could find biomarkers for these gene-environment interactions, then perhaps we could develop a simple blood test that identifies people who are at high risk of cancer from low-dose radiation," says Mao.
-end-
The research was supported by the Department of Energy's Office of Science (Office of Biological and Environmental Research).

Lawrence Berkeley National Laboratory addresses the world's most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab's scientific expertise has been recognized with 13 Nobel prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy's Office of Science. For more, visit http://www.lbl.gov. DOE's Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit the Office of Science website at science.energy.gov/.

DOE/Lawrence Berkeley National Laboratory

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.