phosphorus-radioisotopes and Colorectal-Neoplasms

Cancers have been revealed to be extremely heterogenous in terms of the frequency and types of mutations present in cells from different malignant tumors. Thus, it is likely that uniform clinical treatment is not optimal for all patients, and that the development of individualized therapeutic regimens may be beneficial. We describe the generation of multiple, unique small peptides nine to thirty-four amino acids in length which, when labeled with the radioisotope (32)P, bind with vastly differing efficiencies to cell lines derived from different colon adenocarcinomas. In addition, the most effective of these peptides permanently transfers the (32)P radioisotope to colorectal cancer cellular proteins within two hours at a rate that is more than 150 times higher than in cell lines derived from other cancers or from the normal tissues tested. Currently, the only two FDA-approved radioimmunotherapeutic agents in use both employ antibodies directed against the B cell marker CD20 for the treatment of non-Hodgkin's lymphoma. By using the method described herein, large numbers of different (32)P-labeled peptides can be readily produced and assayed against a broad spectrum of cancer types. This report proposes the development and use of (32)P-labeled peptides as potential individualized peptide-binding therapies for the treatment of colon adenocarcinoma patients.

Topics: Adenocarcinoma; Autoradiography; Cell Line, Tumor; Colorectal Neoplasms; Electrophoresis, Polyacrylamide Gel; Humans; Peptides; Phosphorus Radioisotopes; Phosphorylation

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.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinogens; Colon; Colorectal Neoplasms; DNA; Female; Humans; Infant, Newborn; Intestinal Mucosa; Isotope Labeling; Male; Middle Aged; Phosphorus Radioisotopes; Rectum; Sensitivity and Specificity

The incidence of colorectal cancer in the western hemisphere is though to be the result, in part, of environmental agents, and many studies strongly implicate diet as a determining factor. It is conceivable that the ingestion of genotoxic chemicals present in food or the endogenous formation of such substances in the gut may initiate colorectal cancer in humans. In the present study, 32P-postlabelling has been used to examine DNA from normal-appearing colonic mucosa obtained from (i) patients undergoing surgery for colorectal cancer and (ii) adult and fetal controls for the presence of aromatic DNA adducts.

Topics: Colon; Colorectal Neoplasms; DNA; Female; Humans; Intestinal Mucosa; Middle Aged; Phosphorus Radioisotopes