Effects of acetaldehyde on cell regeneration and differentiation of the upper gastrointestinal tract mucosa.
BACKGROUND
The tumor-promoting effect of ethanol on cancer of the upper respiratory-digestive tract is not well understood. Although ethanol itself is not carcinogenic, the first product of ethanol metabolism-acetaldehyde is. Acetaldehyde can be produced from ethanol by oral bacteria, and high concentrations have been observed in human saliva after ethanol consumption. The purpose of this study was to investigate whether acetaldehyde administered orally to rats induces altered differentiation and proliferation in the animals' upper gastrointestinal tracts.


METHODS
Twenty Wistar rats were given either water containing acetaldehyde at a concentration of 120 mM or tap water to drink for 8 months. Tissue specimens were then taken from the tongue, epiglottis, and forestomach of each animal and immunohistochemically stained for markers of cellular proliferation (Ki67 nuclear antigen) or differentiation (cytokeratins 1, 4, 10, 11, 14, and 19). The mean epithelial thickness of each sample was measured via light microscopy, using an eyepiece containing grid lines. Differences between the control and acetaldehyde-treated groups were analyzed by use of the unpaired Student's t test. All reported P values are two-sided.


RESULTS
Although no tumors were observed, staining for cytokeratins 4 and 14 revealed an enlarged basal layer of squamous epithelia in the rats receiving acetaldehyde. In these animals, cell proliferation was significantly greater than that observed in the control animals for samples from the tongue (P<.0001), epiglottis (P<.001), and forestomach (P<.0001). In addition, the epithelia from acetaldehyde-treated rats were significantly thicker than in epithelia from control animals (P<.05 for all three sites).


CONCLUSIONS
Acetaldehyde, administered orally to rats, can cause hyperplastic and hyperproliferative changes in epithelia of the upper gastrointestinal tract. This finding suggests that microbially produced acetaldehyde in saliva may explain the tumor-promoting effect of ethanol on these epithelia.
Homann
N
N
Research Unit of Alcohol Diseases, University Central Hospital of Helsinki, Finland.
Kärkkäinen
P
P
Koivisto
T
T
Nosova
T
T
Jokelainen
K
K
Salaspuro
M
M
D000079:Acetaldehyde / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002453:Cell Cycle / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects* / Q000473:pathology*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D000431:Ethanol / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005931:Glottis / Q000187:drug effects / Q000473:pathology; D007633:Keratins / Q000032:analysis*; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014059:Tongue / Q000187:drug effects / Q000473:pathology
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D000431:Ethanol; D007633:Keratins; D000079:Acetaldehyde