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저자： 업로드：2017-06-06 조회수：
A common class of chemicals
found everywhere from car exhausts, smoke, building materials and furniture to
cosmetics and shampoos could increase cancer risk because of their ability to
break down the repair mechanisms that prevent faults in our genes, according to
a study published today in the journal Cell.
Damage to our DNA arises frequently as our cells divide, and it can lead to the development of cancers. Fortunately, the body has its own defense mechanism that helps repair this damage. This defense mechanism, however, is obstructed by chemicals of the aldehyde class. According to a new study, aldehyde exposure impedes DNA repair, even in normal healthy cells, but people who have inherited a faulty copy of BRCA2 are particularly sensitive to such damage.
The study was led by Ashok Venkitaraman, Ph.D., director of the Medical Research Council Cancer Unit at the University of Cambridge. Prof. Venkitaraman and colleagues used genetically engineered human cells and cells from patients bearing a faulty copy of the breast cancer gene BRCA2 to identify the mechanism by which exposure to aldehydes could promote cancer.
Details of this work appeared June 1 in the journal Cell, in an article entitled “A Class of Environmental and Endogenous Toxins Induces BRCA2 Haploinsufficiency and Genome Instability.” The article reports that exposure to naturally occurring concentrations of formaldehyde or acetaldehyde selectively unmasks genomic instability in cells heterozygous for multiple, clinically relevant, truncating BRCA2 mutations.
“Naturally occurring concentrations of formaldehyde, a product of cellular metabolism and a ubiquitous environmental toxin, provoke replication fork instability and structural chromosomal aberrations in cells heterozygous for multiple, pathogenic truncating mutations affecting the BRCA2 tumor suppressor,” wrote the article’s authors. “These anomalies arise from a previously unrecognized effect of formaldehyde to selectively deplete BRCA2 via proteasomal degradation. ... Similar effects occur with acetaldehyde, a product of ethanol catabolism.”
These findings could help explain why people who inherit a single faulty copy of the BRCA2 gene are susceptible to cancer. Cells should be able to repair DNA using the lower—but still adequate—levels of BRCA2 protein made from the remaining intact copy of the gene. But that doesn’t always happen.
This new study shows that
aldehydes trigger the degradation of BRCA2 protein in cells. In people who
inherit one faulty copy of the BRCA2 gene, this effect
