Chromosomal instability and radiosensitivity in myelodysplastic syndrome cells.
Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells. To investigate whether chromosomal instability and/or DNA repair defects are involved in the development of MDS, we measured the micronucleus (MN) frequency in peripheral blood lymphocytes exposed to various doses of X-rays, using a cytokinesis-block micronucleus assay. The spontaneous MN frequencies in RAEB and RAEB-T patients were significantly higher than those in normal individuals (P = 0.0224, P = 0.008, respectively). Also, the X-ray-induced MN frequencies in RA/RARS, RAEB, and RAEB-T patients were significantly higher than those in normal individuals (P = 0.007, P = 0.003, P = 0.003, respectively, at 2 Gy). In order to elucidate the cause of unusual radiosensitivity, we measured the expression levels of nucleotide excision repair (NER) genes in peripheral blood mononuclear cells using a RT-PCR method. Reduction of NER gene expression was found in only one of 10 patients with low risk MDS, but in four of 11 patients with high risk MDS. Our data suggest that chromosomal instability and DNA repair defects may be involved in the pathophysiology of disease progression of MDS.
Kuramoto
K
K
Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan.
Ban
S
S
Oda
K
K
Tanaka
H
H
Kimura
A
A
Suzuki
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D017931:DNA Primers / Q000737:chemistry; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D029721:Drosophila Proteins / Q000235:genetics; D004720:Endonucleases; D005260:Female; D006801:Humans; D007621:Karyotyping; D008214:Lymphocytes / Q000097:blood / Q000473:pathology; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000532:radiotherapy*; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D011836:Radiation Tolerance; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014965:X-Rays; D000099250:DNA Excision Repair Protein ERCC-5
D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C078672:hay protein, Drosophila; C086984:XPC protein, human; C071447:ERCC1 protein, human