Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017, Medical Research Council
Credit: CC0 Public Domain

New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing cancer therapies, according to research led by scientists from the Medical Research Council (MRC) Laboratory of Molecular Biology.

The research, published in Nature, has uncovered that formaldehyde is a by-product of a key process called the 'one carbon '. This cycle uses a vitamin - folate - to create DNA and essential amino acids, which need to function and multiply.

Dr Ketan Patel, senior author on the paper from the MRC Laboratory of Molecular Biology, said: "We've known for a while that we must produce formaldehyde in our bodies, but we didn't know where it comes from. We've discovered that some of it comes from an unexpected source, a key pathway - called the one carbon cycle - that's used to make the building blocks of life, such as DNA and certain amino acids. The one-carbon cycle is a fundamental process which is present in all forms of life, right down to bacteria."

Formaldehyde is a toxin because it can damage DNA. However, our cells have two lines of defence against the danger of formaldehyde. Firstly, an enzyme converts the formaldehyde into a less dangerous chemical, called formate. And secondly, DNA damage caused by formaldehyde can be fixed by DNA repair enzymes.

These findings could provide a new target for developing cancer drugs, as some types of cancer - notably BRCA1 or BRCA2 breast cancers - lack the DNA repair enzymes to protect themselves from formaldehyde toxicity. The researchers found that treating laboratory-grown cells with folate leads to the release of formaldehyde, and speculate this could lethally damage the DNA of the BRCA that cannot repair this damage. Healthy surrounding cells would not be damaged since they have functioning DNA repair mechanisms.

Dr Patel commented: "The one carbon cycle is already a key target for cancer drugs and this study opens up exciting new opportunities to harness this pathway for cancer research."

Dual action

The scientists were surprised to find that the toxic formaldehyde also has a positive function in cells, as it paradoxically also fuels the one-carbon cycle. Formaldehyde is broken down into formate, which the one-carbon cycle uses to make the building blocks of life.

Dr Patel said: "Surprisingly, although the body produces this violently toxic formaldehyde, it then converts it into something that can be used to fuel the one-carbon cycle. So, something toxic is converted into something useful to the body, to make certain amino acids and DNA. Folate and formaldehyde have two faces: a beneficial side because they provide the chemical buildings blocks for cells to live and grow, and a dangerous side because formaldehyde can damage DNA."

This discovery suggests how cancer cells may be able to resist current chemotherapy drugs, such as methotrexate, that block folate going into the one . The researchers suggest that with folate pathway blocked, cancer cells might be able to keep functioning by switching to using the newly discovered formaldehyde pathway to build the DNA and proteins that cancer cells need to multiply.

Dr Nathan Richardson, MRC Head of Molecular and Cellular Medicine, said: "This study is a great example of the value of investing in discovery science, where important insights into cellular metabolism have opened up new opportunities for treating interventions in diseases, such as and overcoming resistance to existing therapies."

While the study shows that increased input of folate results in greater formaldehyde toxicity, it was conducted in laboratory cell cultures dosed with high amounts of folate and genetically altered so that they cannot process . The authors caution that no conclusions should be drawn about whether there is any overall effect in a living animal consuming .

Explore further: Formaldehyde damages proteins, not just DNA

More information: Guillermo Burgos-Barragan et al, Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism, Nature (2017). DOI: 10.1038/nature23481

Related Stories

Formaldehyde damages proteins, not just DNA

September 29, 2016
The capacity of formaldehyde, a chemical frequently used in manufactured goods such as automotive parts and wood products, to damage DNA, interfere with cell replication and cause cancer inspired new federal regulations this ...

New study challenges formaldehyde cancer findings

May 2, 2017
A newly published reanalysis of raw data from a study widely used by chemical assessment agencies to set hazard assessments for formaldehyde shows no link between formaldehyde exposure and leukemia. The peer-reviewed paper ...

Funeral directors may be at heightened risk of progressive neurodegenerative disease

July 13, 2015
Funeral directors, who prepare bodies for burial, may be at heightened risk of the neurodegenerative disease amyotrophic lateral sclerosis, or ALS for short, as a result of the formaldehyde used in embalming fluid, suggests ...

New cancer therapy eliminates toxic delivery vehicles for microRNA

August 2, 2017
Researchers at Purdue University have discovered a mechanism for delivering tumor-suppressing microRNAs that eliminates the need for toxic delivery vehicles.

Exposure to toxins in e-cig vapor varies depending on scenario

August 2, 2017
E-cigarettes are often perceived to be less harmful than their traditional counterparts, but they could still expose the people who "vape" and those around them to harmful compounds. Researchers now report in ACS' journal ...

Recommended for you

New therapeutic gel shows promise against cancerous tumors

February 21, 2018
Scientists at the UNC School of Medicine and NC State have created an injectable gel-like scaffold that can hold combination chemo-immunotherapeutic drugs and deliver them locally to tumors in a sequential manner. The results ...

Kinase inhibitor larotrectinib shows durable anti-tumor abilities

February 21, 2018
Three simultaneous safety and efficacy studies of the drug larotrectinib reported an overall response rate of 75 percent for patients ages four months to 76 years with 17 different cancer diagnoses. All patients had tumors ...

Five novel genetic changes linked to pancreatic cancer risk

February 21, 2018
In what is believed to be the largest pancreatic cancer genome-wide association study to date, researchers at the Johns Hopkins Kimmel Cancer Center and the National Cancer Institute, and collaborators from over 80 other ...

Similarities found in cancer initiation in kidney, liver, stomach, pancreas

February 21, 2018
Recent research at Washington University School of Medicine in St. Louis demonstrated that mature cells in the stomach sometimes revert back to behaving like rapidly dividing stem cells. Now, the researchers have found that ...

Research could change how doctors treat leukemia and other cancers fed by fat

February 21, 2018
Obesity and cancer risk have a mysterious relationship, with obesity increasing the risk for 13 types of cancer. For some cancers—including pediatric cancers—obesity affects survival rates, which are lower for people ...

New technique predicts gene resistance to cancer treatments

February 21, 2018
Yale School of Public Health researchers have developed a new method to predict likely resistance paths to cancer therapeutics, and a methodology to apply it to one of the most frequent cancer-causing genes.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.