Event: CoAS Research Days 2014
Presentation Type: Poster
Title: Role of alcohol detoxification in preventing DNA damage
Abstract:
Acetaldehyde, the primary metabolite of alcohol, is responsible for hangovers and is a potential carcinogen due to its ability to induce cross-links in DNA. These cross-links disrupt the DNA replication process, causing DNA damage and genomic instability, which is a hallmark of cancer. Humans normally possess genes specialized for the detoxification of this harmful chemical into harmless acetic acid. However, a large percentage of the East Asian population has a variant of the acetaldehyde dehydrogenase gene ALDH2. These individual are unable to efficiently catalyze this detoxification reaction, resulting in an alcohol flush reaction, which is associated with reddening of the face due to capillary dilation brought on by the accumulation of acetaldehyde in the body, as well as increased risks of esophageal and intestinal cancers. To investigate the effect of aldehydes in DNA damage response, we have identified and characterized three acetaldehyde dehydrogenases and three formaldehyde dehydrogenases in a model organism Schizosaccharomyces pombe. Cells with mutations in any of these genes displayed hypersensitivity to acetaldehyde or formaldehyde. When compared to wild-type cells, these mutants displayed a significant increase in DNA damage in response to aldehydes. These data indicate the requirement of alcohol dehydrogenase-related genes for preventing DNA damage.
Presentation Type: Poster
Title: Role of alcohol detoxification in preventing DNA damage
Abstract:
Acetaldehyde, the primary metabolite of alcohol, is responsible for hangovers and is a potential carcinogen due to its ability to induce cross-links in DNA. These cross-links disrupt the DNA replication process, causing DNA damage and genomic instability, which is a hallmark of cancer. Humans normally possess genes specialized for the detoxification of this harmful chemical into harmless acetic acid. However, a large percentage of the East Asian population has a variant of the acetaldehyde dehydrogenase gene ALDH2. These individual are unable to efficiently catalyze this detoxification reaction, resulting in an alcohol flush reaction, which is associated with reddening of the face due to capillary dilation brought on by the accumulation of acetaldehyde in the body, as well as increased risks of esophageal and intestinal cancers. To investigate the effect of aldehydes in DNA damage response, we have identified and characterized three acetaldehyde dehydrogenases and three formaldehyde dehydrogenases in a model organism Schizosaccharomyces pombe. Cells with mutations in any of these genes displayed hypersensitivity to acetaldehyde or formaldehyde. When compared to wild-type cells, these mutants displayed a significant increase in DNA damage in response to aldehydes. These data indicate the requirement of alcohol dehydrogenase-related genes for preventing DNA damage.