Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Maintenance: Tuesday, 5.7.2016, 07:00-08:00

Maintenance work on ZORA and JDB on Tuesday, 5th July, 07h00-08h00. During this time there will be a brief unavailability for about 1 hour. Please be patient.

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-35321

Hofstetter, B; Niemierko, A; Forrer, C; Benhattar, J; Albertini, V; Pruschy, M; Bosman, F T; Catapano, C V; Ciernik, I F (2010). Impact of genomic methylation on radiation sensitivity of colorectal carcinoma. International Journal of Radiation Oncology, Biology and Physics, 76(5):1512-1519.

[img] PDF - Registered users only
View at publisher


PURPOSE: To investigate the influence of demethylation with 5-aza-cytidine (AZA) on radiation sensitivity and to define the intrinsic radiation sensitivity of methylation deficient colorectal carcinoma cells. METHODS AND MATERIALS: Radiation sensitizing effects of AZA were investigated in four colorectal carcinoma cell lines (HCT116, SW480, L174 T, Co115), defining influence of AZA on proliferation, clonogenic survival, and cell cycling with or without ionizing radiation. The methylation status for cancer or DNA damage response-related genes silenced by promoter methylation was determined. The effect of deletion of the potential target genes (DNMT1, DNMT3b, and double mutants) on radiation sensitivity was analyzed. RESULTS: AZA showed radiation sensitizing properties at >or=1 micromol/l, a concentration that does not interfere with the cell cycle by itself, in all four tested cell lines with a sensitivity-enhancing ratio (SER) of 1.6 to 2.1 (confidence interval [CI] 0.9-3.3). AZA successfully demethylated promoters of p16 and hMLH1, genes associated with ionizing radiation response. Prolonged exposure to low-dose AZA resulted in sustained radiosensitivity if associated with persistent genomic hypomethylation after recovery from AZA. Compared with maternal HCT116 cells, DNMT3b-defcient deficient cells were more sensitive to radiation with a SER of 2.0 (CI 0.9-2.1; p = 0.03), and DNMT3b/DNMT1-/- double-deficient cells showed a SER of 1.6 (CI 0.5-2.7; p = 0.09). CONCLUSIONS: AZA-induced genomic hypomethylation results in enhanced radiation sensitivity in colorectal carcinoma. The mediators leading to sensitization remain unknown. Defining the specific factors associated with radiation sensitization after genomic demethylation may open the way to better targeting for the purpose of radiation sensitization.


25 citations in Web of Science®
26 citations in Scopus®
Google Scholar™



1 download since deposited on 09 Aug 2010
0 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Radiation Oncology
Dewey Decimal Classification:610 Medicine & health
Date:April 2010
Deposited On:09 Aug 2010 10:23
Last Modified:05 Apr 2016 14:13
Publisher DOI:10.1016/j.ijrobp.2009.10.037
PubMed ID:20338477

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page