Lymphocyte telomere dynamics and telomerase activity in inflammatory bowel disease: effect of drugs and smoking.
BACKGROUND
The chromosome instability observed in peripheral blood lymphocytes in ulcerative colitis could be a biomarker of cancer susceptibility.


OBJECTIVE
To determine whether accelerated telomere shortening could explain chromosome instability and assess the effect of drugs and smoking on telomere dynamics in these cells.


METHODS
Peripheral blood lymphocytes were isolated from ulcerative colitis, Crohn's disease and non-inflammatory bowel disease control patients. Telomere lengths were measured by quantitative real-time polymerase chain reaction. After activation and cell separation, telomerase activity and human telomerase reverse transcriptase messenger ribonucleic acid were measured by telomerase repeat amplification protocol enzyme-linked immunosorbent serological assay and quantitative real-time polymerase chain reaction, respectively.


RESULTS
Age-related telomere loss in peripheral blood lymphocytes was similar in ulcerative colitis, Crohn's disease and control patients. Telomerase activity decreased with age in all groups and correlated positively with telomere length (r = 0.489, P = 0.006). Among Crohn's disease patients, azathioprine was associated with decreased telomerase activity (0.66 vs. 1.54, P = 0.026, P < 0.05) and smoking was associated with decreased human telomerase reverse transcriptase mRNA expression (10.5 vs. 33.3, P = 0.036, P < 0.05).


CONCLUSIONS
Telomere shortening is not accelerated and therefore cannot be the cause of the chromosome instability observed in ulcerative colitis peripheral blood lymphocytes. Azathioprine and cigarette smoking modify telomerase expression in these cells.
Getliffe
K M
KM
Department of Biological Sciences, University of Warwick, Coventry, UK.
Al Dulaimi
D
D
Martin-Ruiz
C
C
Holder
R L
RL
von Zglinicki
T
T
Morris
A
A
Nwokolo
C U
CU
D000328:Adult; D000368:Aged; D000963:Antimetabolites / Q000494:pharmacology; D001379:Azathioprine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology*; D008214:Lymphocytes / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012907:Smoking / Q000378:metabolism*; D019098:Telomerase / Q000187:drug effects / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*
D000963:Antimetabolites; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase; D001379:Azathioprine