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Study links formaldehyde to protein damage

U. researcher discovers potential explanation for formaldehyde’s neurotoxic effects in co-led study

Formaldehyde, a known toxicant and carcinogen, is more harmful than previously believed, according to a study co-authored by Anatoly Zhitkovich, professor of pathology and laboratory medicine at the Warren Alpert Medical School. The study, published Sept. 14 in the American Journal of Pathology, suggests that formaldehyde damages proteins as well as DNA, a finding that has serious implications for human health.


The study was originally designed to explore how formaldehyde damages DNA because formaldehyde has long been known to cause cell damage, DNA damage and cancer. But during the study, “coincidental findings” led the authors to believe that formaldehyde harms cells in a second way by significantly damaging proteins, wrote Caitlin McCarthy, a co-author of the study, in an email to The Herald.


The findings were “exciting,” McCarthy wrote, because this is the first study to show formaldehyde’s effects on proteins.


When the researchers were studying the effects of formaldehyde on DNA, they noticed that the levels of an anticancer protein, p53, unexpectedly began to decrease as the doses of formeldahyde increased. This suggested that formaldehyde was somehow preventing the anticancer protein from protecting the cell properly, and that was the first sign of possible protein damage, Zhitkovich said. 


The researchers evaluated the severity of the protein damage by examining how many proteins the cell kills because the proteins could not be repaired, Zhitkovich said. The study found that there were “massive amounts” of polyubiquitination, or an extremely large build-up of damaged proteins that had been marked for destruction, he added.


The study showed that formaldehyde acts as a “heat shock mimic.” It triggers the same biological response as heat and causes the proteins to misfold and mutate. The results “open a window in some previously unrecognized form of injury to cells,” Zhitkovich said. 


The study is “significant because it has direct links to human health and well-being,” McCarthy wrote. “People can suffer occupational exposure to formaldehyde, and it is used in many manufactured products.”


His team thinks the data provides an explanation for the neurotoxic effects of formaldehyde, Zhitkovich added. High doses of formaldehyde have been known to cause Parkinson’s disease, eyesight damage and other diseases that stem from nerve damage, but the reason was unknown. The study’s results suggest that the formaldehyde-caused injury to proteins engenders the neurotoxic effects.


“Accumulation of large volumes of protein damage is one of the trademarks of many neurodegenerative diseases,” McCarthy wrote.


A relevant question now is whether the formaldehyde that humans naturally produce could have harmful long-term effects, Zhitkovich said. It is possible that this internal source of formaldehyde would significantly damage DNA and proteins, which would contribute to age-related health problems as cells age and unrepaired damages accumulate over a lifetime, he added.   


This study should influence people to “minimize their exposure” to formaldehyde, McCarthy wrote. But the chemical is used in many common items such as new carpets, paints, household and cosmetic products and new mobile home building materials, according to the researchers. The study might lead to “new regulations that limit the use of formaldehyde in these products,” wrote Sara Ortega-Atienza, lead author of the study, in an email to The Herald.


It can be “scary” to consider the significant effects of formaldehyde from cigarette smoke, indoor offices and especially in occupational settings, Zhitkovich said. People who smoke cigarettes or are professionally exposed to formaldehyde, such as embalmers, are at a significantly higher risk for cancer, he added.


People who are professionally exposed to formaldehyde should be careful to use their companies’ protective equipment properly, McCarthy wrote. “Industries that use formaldehyde in their manufacturing should considering switching to less harmful alternatives,” McCarthy added.

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