Background: Disinfection byproducts (DBPs) from chlorinated drinking water have been linked to an increased risk of cancer in the bladder, stomach, colon, and rectum. No studies showed the independent trends and prevalence of these cancers in Ethiopia. Therefore, this study aimed to determine the prevalence and trends of disinfection byproducts-related cancers in Addis Ababa, Ethiopia. Methods: Data were collected from the Addis Ababa Cancer Registry. Spatial data sets were produced and classified into households receiving chlorinated surface water and less chlorinated groundwater. The Cochran-Armitage trend test was used to evaluate whether there was a disinfection byproducts-related cancers (DBRCs) trend among communities receiving chlorinated water. Negative binomial regression was used to analyze the incidence rate. Results: A total of 11, 438 cancer cases were registered between 2012 and 2016, and DBRCs accounted for approximately 17%. The majority of the total cancer cases were female; 7,706 (67%). The prevalence of DBRCs was found to be higher in communities supplied with chlorinated water. From 2012 to 2016, the trend of colon cancer increased (β = 10.3, P value = .034); however, esophageal cancer decreased (β = −6.5, P value = .018). Approximately 56% of colorectal cancer patients and 53% of stomach cancer patients are known to be using chlorinated surface water for drinking regularly. In addition, approximately 57.1% and 54% of kidney and bladder cancer patients, respectively, used chlorinated surface water. Conclusion: The prevalence of DBRCs in this study was found to be high. The colon cancer trend increased substantially from 2012 to 2016. The prevalence of DBRCs was higher in communities supplied with chlorinated surface water. Similarly, the prevalence of DBRCs was higher among males than females. Further study is required to validate the association between DBRCs and water chlorination.

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Under the hypotheses of a structurally related binding site for antagonists of G-protein coupled receptors and the ability of cyclic pentapeptides of chiral sequence D1L2D3D4L5 to form rigid structures with which probe the pharmacophoric specificity of these receptors, inhibitors of substance P were designed based on available structure-activity relationships. ITF 1565, cyclo[D-Trp1-Pro2-D-Lys3-D-Trp4-Phe5], antagonized substance P activity mediated by type 1 neurokinin receptor (NK1) whereas it acted weakly against NK2 and did not inhibit endothelin at all. The preferential conformation of the peptide was obtained from nmr spectroscopy and computer calculations, and shown to contain the same beta II-turn and gamma'-turn found in other cyclic pentapeptides with the same chiral sequence. The structure of the peptide was compared with that of the beta-D-glucose molecule that has been proposed as a semirigid scaffold for antagonists of G-protein coupled receptors. The gamma'-turn of the cyclic peptide superimposed well with beta-D-glucose in the chair conformation. Furthermore, when the side chains were considered, the aromatic groups of the two molecules were found to generally overlap. These results support the view of G-protein coupled receptors as possessing structurally similar binding sites for antagonists and suggest that cyclic pentapeptides of chiral sequence D1L2D3D4L5 may be useful as semirigid scaffolds for the design of antagonists of this family of receptors.

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