Presence of mucosa-specific DNA adduct in human colon: possible implication for colorectal cancer.
DNA of normal mucosa and the adjacent muscular layer from 18 adults suffering from colorectal neoplasms was examined by 32P-post-labeling analysis in order to estimate the exposure of the human colon and rectum to environmental carcinogens. Colorectal DNA samples obtained from six newborns were also examined as a normal control because they were presumed to have been minimally exposed to environmental carcinogens. One common mucosa-specific DNA adduct was found in the normal colorectal wall in all adults at the level of 0.10-34.13 adducts/10(8) nucleotides (mean +/- SD: 3.64 +/- 7.92 adducts/10(8) nucleotides), however, these were absent from the newborns' colons. Although several common spots were present in the mucosa, muscular layer and newborn tissues, there was no muscular layer-specific DNA adduct. The relationship between the levels of the mucosa-specific DNA adduct in the non-cancerous part and the histological degree of malignancy was not significant. The presence of this mucosa-specific DNA adduct in adult colon suggests that the human colon is commonly exposed mainly to one environmental carcinogen. This carcinogen is supposed to originate from foods, because the incidence of colorectal carcinoma is closely linked to dietary habits and the mucosa-specific DNA adduct was not present in newborns who had never ingested food. The incidence of adult colonic cancer originating from its mucosa is high, while cases of muscular origin or in newborn colon are rare. Therefore, the mucosa-specific DNA adduct is presumably responsible for the development of colonic cancer of epithelial origin.
Umemoto
A
A
Second Department of Surgery, School of Medicine, University of Tokushima, Japan.
Kajikawa
A
A
Tanaka
M
M
Hamada
K
K
Seraj
M J
MJ
Kubota
A
A
Nakayama
M
M
Kinouchi
T
T
Ohnishi
Y
Y
Yamashita
K
K
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002273:Carcinogens / Q000032:analysis* / Q000378:metabolism* / Q000633:toxicity; D003106:Colon / Q000737:chemistry*; D015179:Colorectal Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D007553:Isotope Labeling; D008297:Male; D008875:Middle Aged; D010761:Phosphorus Radioisotopes; D012007:Rectum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012680:Sensitivity and Specificity
D002273:Carcinogens; D010761:Phosphorus Radioisotopes; D004247:DNA