11 July 2011
ByAppeared in BioNews 615
Alcohol can cause irreparable DNA damage and fetal abnormalities in pregnant mice, a study has found. The findings may explain how excessive drinking during pregnancy causes fetal alcohol syndrome, which can lead to lifelong learning disabilities.
The study is the first showing how excess alcohol can damage DNA, according to a Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) press release.
'We have long suspected that alcohol causes DNA damage but there has not until now been any direct evidence to support this. This is the first direct evidence that alcohol can cause DNA mutations', Dr Ketan Patel, group leader at the MRC LMB in Cambridge, UK and lead study author, said in The Independent.
Dr Patel's team found cells are normally protected from damaging effects of alcohol by enzymes produced by the Aldh2 gene that break down the chemical acetaldehyde, a toxic product of alcohol. If this fails, acetaldehyde builds up and can damage DNA, but enzymes from the Fancd2 gene, called Fanconi proteins, can repair this DNA damage.
Pregnant mice genetically modified to lack both of these defence mechanisms were extremely sensitive to alcohol. If their fetuses were also lacking both genes, they were less likely to survive to birth if exposed to alcohol. Forty-three percent of the surviving fetuses had eye abnormalities and 29 percent had brain defects reminiscent of fetal alcohol syndrome.
Unlike these mice, in most people the two defence mechanisms are working normally. The next step of this research would be to see what role DNA damage is playing in fetal alcohol syndrome in humans.
'Our work suggests that binge drinking could generate enough acetaldehyde to overwhelm the body's two natural defence mechanisms. This new knowledge transforms our view of precisely how excess alcohol causes damage - ultimately changing our DNA', said Dr Patel.
The research also has implications for people with Fanconi anaemia, a rare disease caused by mutations in the Fancd2 gene where people lack functional Fanconi proteins. These people are at high risk of DNA damage from acetaldehyde which, the authors suggest, may explain their increased susceptibility to blood disorders and cancer.
This research was published in the journal Nature.