Transcriptomic profiling of radiation-resistant or -sensitive human colorectal cancer cells: Acute effects of a single X-radiation dose

Abstract

We previously isolated several clones that were closely-related genetically from a human colorectal tumor (HCT116) cell line. These clones displayed significantly different X-radiation response phenotypes. In this paper, we investigated how a single dose of X-radiation modulated the transcriptomic profiles of either the radiation-resistant (HCT116Clone2_XRR) or the radiation-sensitive (HCT116CloneK_XRS) clone when each was compared to a reference clone, HCT116Clone10_control. The latter represented a control clone that displayed a similar X-radiation response as the parental HCT116 cells. Pooled RNAs were obtained from HCT116Clone2_XRR, HCT116CloneK_XRS or HCT116Clone10_control cells either before or at 10 min, 6 or 24 h after treatment with 4-Gy X-radiation. Transcriptomic profiles were assessed by cDNA microarrays. At least three independent experiments were carried out for each time point and statistical analysis was performed by paired t-test (p<0.05). From 19,200 genes/ESTs examined, we identified only 120 genes/ESTs that were differentially expressed at any one of these four time points. Interestingly, different patterns of gene modulation were observed between the radiation-sensitive and radiation-resistant clones. However, the fold changes of gene modulation were generally small (2-3 fold). Surprisingly, only 12.7% of 79 genes involved in DNA damage sensor/repair and cell cycle and between 2.6 and 9.2% of 76 genes involved in apoptosis, were significantly modulated in these early time points following irradiation. By comparison, up to 10% of 40 known housekeeping genes were differentially expressed. Thus in our experimental model, we were able to detect the up-regulation or down-regulation of mostly novel genes and/or pathways in the acute period (up to 24 h) following a single dose of 4-Gy X-radiation.