Acute high-dose X-radiation-induced genomic changes in A549 cells.

Accidents with ionizing radiation often involve single, acute high-dose exposures that can lead to acute radiation syndrome and late effects such as carcinogenesis. To study such effects at the cellular level, we investigated acute ionizing radiation-induced chromosomal aberrations in A549 adenocarcinoma cells at the genome-wide level by exposing the cells to an acute dose of 6 Gy 240 kV X rays. One sham-irradiated clone and four surviving irradiated clones were recovered by minimal dilution and further expanded and analyzed by chromosome painting and tiling-path array CGH, with the nonirradiated clone 0 serving as the control. Acute X-ray exposure induced specific translocations and changes in modal chromosome number in the four irradiated clones. Array CGH disclosed unique and recurrent genomic changes, predominantly losses, and revealed that the fragile sites FRA3B and FRA16D were preferential regions of genomic alterations in all irradiated clones, which is likely related to radioresistant S-phase progression and genomic stress. Furthermore, clone 4 displayed an increased radiosensitivity at doses >5 Gy. Pairwise comparisons of the gene expression patterns of all irradiated clones to the sham-irradiated clone 0 revealed an enrichment of the Gene Ontology term "M Phase" (P = 6.2 × 10(-7)) in the set of differentially expressed genes of clone 4 but not in those of clones 1-3. Ionizing radiation-induced genomic changes and fragile site expression highlight the capacity of a single acute radiation exposure to affect the genome of exposed cells by inflicting genomic stress.

Modified "cup-patch" ileocystoplasty for urinary bladder reconstruction in a dog.

Full-thickness wall necrosis involving 90 to 95% of the urinary bladder was diagnosed in a 6-month-old Golden Retriever 2 days after ovariohysterectomy. An isolated, vascularized segment of ileum denuded of mucosa was used to reconstruct the urinary bladder. Serial excretory urography over 1 year indicated gradual enlargement of the bladder, with development of a smooth mucosal surface. At 6 months after reconstructive surgery, the dog was voiding urine 2 to 3 times/d and was continent. Results of renal function testing, urinalysis, and bacteriologic culture of urine were all considered normal on follow-up examinations. The cause of bladder wall necrosis was never determined. Ileocystoplasty as described herein appears to be an effective urinary bladder reconstructive procedure in dogs whenever the bladder neck, proximal portion of the urethra, and their neurovascular supply can be spared.