Decreased efficiency of gamma-ray-induced DNA double-strand break rejoining in malignant transformants of human bronchial epithelial cells generated by alpha-particle exposure.
OBJECTIVE
To investigate the cytogenetic changes and DNA double-strand break (DSB) rejoining of transformed cell lines generated from human bronchial epithelial cells by alpha-particle exposure.


METHODS
Transformed cell lines were derived from the HPV 18-immortalized human bronchial epithelial cell line BEP2D generated by 1.5 Gy of alpha-particles emitted by a 238Pu source. Two cell lines, BERP35T1 and BERP35T4, were investigated. Karyotypes were analyzed by trypsin/Giemsa banding. Cell survival was estimated by colony assay. PFGE was used to detect the DNA DSB. mRNA expression was analyzed by RT-PCR.


RESULTS
Abnormal chromosomes 2 and 12 with elongated long arm and deletions of chromosomes 2, 12, 13 and 17 were observed in the transformed cell lines. BERP35T4 showed a much higher proportion of polyploid cells (40.5%) compared with parental BEP2D cells and the BERP35TI cell line (5%). BERP35T1 and BERP35T4 showed a markedly lower capacity for rejoining of gamma-ray-induced DNA DSB and increased radiosensitivity compared with parental BEP2D cells. The analysis of mRNA levels revealed a 2.5- to 6.5-fold down-regulated expression of the DNA repair genes XRCC-2, XRCC-3 and Ku80 in BERP35T1 and BERP35T4 cells.


CONCLUSIONS
The karyotypic changes of chromosomes 2, 12, 13 and 17 and the deficiency of DSB rejoining could be related to the malignant transformation processing of BEP2D cells initiated by alpha-particle exposure.
Sun
J F
JF
Department of Radiation Toxicology, Beijing Institute of Radiation Medicine, Beijing, PR China.
Sui
J L
JL
Zhou
P K
PK
Geng
Y
Y
Hu
Y C
YC
Cao
Z S
ZS
Ge
S L
SL
Lou
T Z
TZ
Wu
D C
DC
D000512:Alpha Particles / Q000009:adverse effects; D001980:Bronchi / Q000378:metabolism / Q000528:radiation effects; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000235:genetics / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D007621:Karyotyping; D027383:Papillomaviridae / Q000472:pathogenicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011853:Radiobiology
D012333:RNA, Messenger; D004247:DNA