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Mucosa-specific DNA adducts in human small intestine: a comparison with the colon
K Hamada1, A Umemoto, A Kajikawa
1Second Department of Surgery, School of Medicine, University of Tokushima, Japan.
Abstract:
The presence of several covalent DNA adducts in the human colon was demonstrated by 32P-postlabeling in a previous study. We demonstrated that DNA of all the colonic mucosa tested were selectively adducted by a single genotoxic agent and this modification was completely absent in the DNA of muscular layers. In this study, the DNA adducts of the small intestine are compared with those of the colon to understand the role of mucosa-specific DNA adduct (MSA) in intestinal carcinogenesis. The mucosal DNA of the small intestine from 19 adults undergoing surgery due to gastric carcinoma (seven cases), pancreatic carcinoma (four cases), colon carcinoma (four cases), small intestinal tumor (two cases), intestinal trauma (one case) and ectopic pancreas (one cases) were analyzed. The mucosa-adjacent muscular layer DNA of the corresponding samples was examined as a control. Several common DNA adducts were observed in both mucosal and muscular layers of all the adults. Besides these common background DNA adducts, two MSAs (Si1, Si2) were detected in most of the adults as in colon cases. Si1 was present in all adults examined (19/19 cases) at a level of 0.04-0.22 adducts/10(8) nucleotides (average 0.09) and Si2 was found in 13/19 patients at a level of 0.03-0.08 adducts/10(8) nucleotides (average 0.05). Si2 was the same adduct detected in the adult colonic mucosa. However, they were absent in the adjacent muscular layer as well as in the neonatal intestine tested as a control. The total level of the mucosa-specific DNA adducts of the small intestine was approximately 28-fold lower than that of the colon. Considering that the incidence of cancer in the small intestine is rather lower than that in the colon, these results may be relevant to the development of human intestinal cancer.
Insights
Mucosa-specific DNA adducts (MSAs) were found in the small intestine, similar to the colon, but at lower levels. These findings may link MSAs to intestinal carcinogenesis and lower small intestine cancer rates.
Area of Science:
- Gastroenterology
- Molecular Biology
- Cancer Research
Background:
- Previous studies identified covalent DNA adducts in human colon mucosa.
- These adducts were specific to the mucosal layer, absent in muscular layers.
Purpose of the Study:
- To compare DNA adducts in the small intestine with those in the colon.
- To investigate the role of mucosa-specific DNA adducts (MSAs) in intestinal carcinogenesis.
Main Methods:
- Analysis of mucosal and muscular layer DNA from 19 adult small intestine samples.
- Comparison of DNA adduct profiles between small intestine and colon mucosa.
- Utilized 32P-postlabeling technique for adduct detection.
Main Results:
- Two MSAs (Si1, Si2) were detected in the small intestine mucosa of most adults.
- Si1 was present in all individuals, while Si2 was found in 13/19 patients.
- MSA levels in the small intestine were approximately 28-fold lower than in the colon.
- MSAs were absent in the adjacent muscular layer and neonatal intestine.
Conclusions:
- The presence of MSAs in the small intestine suggests a potential role in intestinal carcinogenesis.
- Lower MSA levels in the small intestine may correlate with its lower cancer incidence compared to the colon.