Evidence of chromosome instability in chronic pancreatitis.
In the current study we analyzed chromosome instability on peripheral blood lymphocytes cultured from 7 untreated patients with chronic pancreatitis (CP) by assessing telomeric associations (TAS), chromosome aberrations (CA) and sister chromatid exchanges (SCE). Seven healthy individuals were also analyzed. Mean frequencies of TAS were significantly higher in CP patients (X +/- SE: 11.00 +/- 2.37) compared to controls (1.00 +/- 0.30) (p<0.001). Chromosomes preferentially involved in TAS were: 9, 20, 16 and 21, being the most affected arms: 9p, 20q, 16p, 9q and 21q. All these terminal bands were coincident with cancer breakpoints (p<0.03), two of them (40%) were specifically associated to pancreatic carcinoma rearrangements. Three bands (60%) were coincident with oncogene location. The mean frequency of CA was significantly higher in patients (3.88 +/- 0.80) compared to controls (0.63 +/- 0.49) (p<0.001). Chromosomes 1, 2 and 13 were the most damaged. No specifically affected breakpoints were found. SCE analysis showed higher levels in patients (8.33 +/- 0.70) than in controls (6.62 +/- 0.34) (p<0.025), but no differences were observed in cell cycle kinetics. Our results clearly indicate that CP patients exhibit chromosome instability, showing the presence of an unstable genome that could be related to the cancer development observed in this disease.
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Dept. de Genética, Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires, Argentina. lacuteci@intramed.net.ar
Fundia
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AF
Morán
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Sosa
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Geldern
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Gómez
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JC
Chopita
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Slavutsky
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D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D002890:Chromosomes, Human, Pair 20; D002891:Chromosomes, Human, Pair 21; D002899:Chromosomes, Human, Pair 9; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D012854:Sister Chromatid Exchange