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Alcohol Effects on Colon Epithelium are Time-Dependent
Faraz Bishehsari1, Lijuan Zhang1, Robin M Voigt1
1Division of Gastroenterology, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois.
Alcoholism, Clinical and Experimental Research
|June 26, 2019
Summary
Timing of alcohol consumption impacts colon cancer risk. Alcohol consumed during rest periods increases DNA damage in the colon, suggesting a critical role for circadian rhythms in alcohol-related carcinogenesis.
Area of Science:
- Gastroenterology
- Molecular Biology
- Cancer Research
Background:
- Alcohol consumption is a known risk factor for colon cancer.
- Circadian disruption may exacerbate alcohol's carcinogenic effects through poorly understood mechanisms.
- Alcohol metabolites, such as acetaldehyde, can cause DNA damage, initiating carcinogenesis.
Purpose of the Study:
- To investigate the influence of the time of alcohol consumption on colonic epithelial tissue damage markers.
- To explore the role of circadian rhythms in alcohol-induced colon carcinogenesis.
- To assess the time-dependent repair efficiency of alcohol-induced DNA damage.
Main Methods:
- Mice were administered alcohol or a control solution at regular intervals over three days.
- Colonic tissues were analyzed for proliferation (Ki67), anti-apoptosis (Bcl-2), DNA damage (γ-H2AX), and acetaldehyde-DNA adducts (N²-ethylidene-dG).
- Circadian disruption was modeled by shifting the light-dark cycle, with subsequent analysis of tissue damage and DNA repair mechanisms, including the role of Xeroderma Pigmentosum Complementation Group A (XPA).
Main Results:
- Alcohol consumption increased colonic epithelial proliferation and DNA damage, with a more pronounced effect during the light (rest) period.
- DNA adduct levels did not significantly vary by time, suggesting reduced DNA repair efficiency during the light phase compared to the dark phase.
- Xeroderma Pigmentosum Complementation Group A (XPA) gene expression exhibited time-dependent regulation, peaking at the onset of the dark period, and XPA-deficient cells showed impaired repair of alcohol-induced DNA damage.
Conclusions:
- The time of day for alcohol intake is a significant factor influencing colon tissue damage and carcinogenic potential.
- Circadian rhythm plays a crucial role in modulating the effects of alcohol on colon carcinogenesis.
- Understanding the time-dependent repair mechanisms is vital for mitigating alcohol-induced colon cancer risk.
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