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PubMed2005

[Monitoring of the radioecological situation of Adjara seacoast].

One of the most important problems of the modern science is the study of biological, physiological and pathological influence of the radiation background on the surrounding environment. The disaster in the Chernobyl Atomic Power Station vitalized and sharpened the problem, as far as after the accident the Black Sea coast was exposed to the pollution. The Radiation background of Adjara seacoast has been studied in Georgia during the period of 1997 to 2002. The level of the radiation background in open areas lowered from 95 hgy/h to 93 hgy/h. The indicators of indoor radiation background have not been essentially changed--110 hgy/h. The average annual dose of irradiation of the population insignificantly lowered from 0,94 mZv/y to 0,937 mZv/y.

Catchment Area, Health↗
PubMed2000

Review of extensive workups of 34 patients overexposed to radiofrequency radiation.

BACKGROUND: The medical records of 34 patients seen at the Aerospace Medicine Directorate, U.S. Air Force Research Laboratory for confirmed exposure to radiofrequency radiation (RFR) exceeding the permitted exposure limits were reviewed to see if RFR overexposure created any detectable clinical or laboratory alterations that could be correlated with power density or the product of power density and time exposed. The goal of this study was to determine which physiological and laboratory parameters required closest attention on work up of future patients with RFR exposure. METHODS: All 34 patients received an extensive history and physical examination, and a large battery of laboratory studies. Clinical findings were also compared with laboratory results. RESULTS: A sensation of warmth was positively associated with power density. A negative correlation was observed between an abnormal tissue destruction screen and power density. Sophisticated neurological tests in 23 patients and extensive psychometric and psychological exams in 30 patients revealed no neurological or ophthalmologic findings attributable to RFR. A few patients reported burning pain that resolved over several weeks; neurological findings were minimal or absent. CONCLUSIONS: Patients with suspected RFR overexposures need to be seen promptly at the nearest medical facility. Based on this study, an extensive evaluation of persons overexposed to non-ionizing radiation should not be routinely performed. However, a careful history and physical examination with laboratory studies as indicated should be performed and the patient's concerns about RFR effects addressed fully.

Adult↗
PubMed2002

Local control of primary Merkel cell carcinoma: review of 45 cases treated with Mohs micrographic surgery with and without adjuvant radiation.

BACKGROUND: Optimal treatment of primary Merkel cell carcinoma (MCC) is unknown. High local recurrence rates after excision alone compel some physicians to advocate postoperative radiation therapy to improve local control. OBJECTIVE: We wondered whether marginal recurrence and survival rates differed between patients with primary MCC treated with Mohs surgery alone and those treated with Mohs surgery and adjuvant postoperative radiation. METHODS: A collaborative retrospective study was performed; the study group consisted of 45 patients with stage I MCC who were histologically and clinically free of disease after Mohs excision. Twenty patients subsequently received elective postoperative radiation to the primary site, and 25 patients had no adjuvant radiation therapy. RESULTS: One marginal recurrence (4%) and 3 in-transit metastases were observed in the Mohs surgery alone group, whereas none were observed in the Mohs surgery and radiation group. The proportion of patients with these events was not significantly different between treatment groups. Overall survival, relapse-free survival, and disease-free survival were not significantly different between treatment groups. CONCLUSION: Adjuvant radiation appears unessential to secure local control of primary MCC lesions completely excised with Mohs micrographic surgery. Adjuvant radiation is recommended for patients unable to have complete excision or if complete histologic margin control is unavailable and should be considered for patients with large or recurrent tumors.

Aged↗
PubMed2005

The importance of abrogation of G2-phase arrest in combined effect of TRAIL and ionizing radiation.

BACKGROUND: In this work we studied the relationship between the enhanced expression of DR5 receptor and the effect of combination of TRAIL and ionizing radiation on cell cycle arrest and apoptosis induction in human leukemia cell line HL-60. MATERIAL AND METHODS: DR5, APO2.7 and cell cycle were analyzed by flow cytometry. Proteins Bid and Mcl-1 were analyzed by Western-blotting. For clonogenic survival, colony assay on methylcellulose was used. RESULTS: Ionizing radiation caused significantly enhanced positivity of DR5 receptors 24 h after irradiation with high doses (6 and 8 Gy). An increase of DR5 receptor positivity after a dose of 2 Gy was not statistically significant and application of TRAIL 48 h after irradiation did not increase the apoptosis induction. However, a decrease of radiation-induced G(2) phase arrest and an increase of apoptosis were observed when TRAIL was applied 16 h before irradiation with the dose of 2 Gy. Incubation with 6 microg/l TRAIL for 16 h reduced D(0) value from 2.9 Gy to 1.5 Gy. The induction of apoptosis by TRAIL was accompanied by Bid cleavage and a decrease of antiapoptotic Mcl-1 16 h after incubation with TRAIL. CONCLUSION: TRAIL in concentration of 6 microg/l applied 16 h before irradiation by the dose of 1.5 Gy caused the death of 63% of clonogenic tumor cells, similarly as the dose of 2.9 Gy alone, which is in good correlation with the enhanced apoptosis induction.

Apoptosis Regulatory Proteins↗
PubMedDate not supplied

Whole-body irradiation and long-term modification of bone marrow-derived cell populations by low- and high-LET radiation.

BACKGROUND: The major aim of this study was to quantify long-term changes in bone marrow-derived cell populations after exposure to radiations of differing quality. MATERIALS AND METHODS: Mice were whole-body irradiated to 2 Gy gamma, proton, carbon or iron radiation, and euthanized approximately 110 days later for immunocyte phenotyping. RESULTS: Splenic lymphocytes and mono/macrophages increased after gamma-rays when compared to 0 Gy and one or more of the other groups. There were high T cells (carbon vs. 0 Gy), high B cells (gamma-rays vs. 0 Gy), and low natural killer (NK) cells (proton and carbon vs. 0 Gy). All radiations, except gamma-rays, increased CD62L+ memory T cell counts, whereas CD62L+ B cells increased only after gamma-rays. CONCLUSION: There were significant aberrations in many immune parameters nearly 4 months after exposure to various forms of radiation. This suggests radiation exposure can have long-term health consequences.

Animals↗
PubMed1976

The role of natural radiations in human leukemogenesis.

Some 3 billion years ago, life arose from a warm pool of primordial ooze amid a constant drizzle of radiation. Steadily, man evolved from the lesser forms of life because of or in spite of his natural background-radiation environment. This study is an attempt to determine to what extent these background radiations are responsible for human disease, namely leukemia. Dose rate data were compared with data on all forms of leukemia in the 50 United States for four population subgroups. For the total U. S., no relation between background radiation and leukemia is apparent. A positive correlation appears, however, if various states are deleted from the analysis. It appears that conditions relative to populations and their environment could mask a radiation effect if in fact one is present.

Background Radiation↗
PubMed2005

Antisense Bcl-2 sensitizes prostate cancer cells to radiation.

BACKGROUND: Bcl-2 is anti-apoptotic and overexpression is associated with prostate tumor aggressiveness. We hypothesized that Bcl-2 has a role in prostate cancer radiation (RT) response. The relationship of Bcl-2 expression in four prostate cancer cell lines, and the effect of modulating expression with a Bcl-2 antisense oligonucleotide (G3139, Genasense, oblimersen sodium, Genta Incorporated), to RT was examined. METHODS: The four cell lines studied were LNCaP (wild type-p53), PC3 (p53 null), Bcl-2 stably transfected LNCaP (LNCaP-BST), and Bcl-2 stably transfected PC3 (PC3-BST) cells. Cells were treated with antisense (AS) Bcl-2 alone or with RT (2-6 Gy). Following RT, cells were processed at 3-6 hr for Western blots, 18 hr for Annexin V staining and flow cytometric analysis, 24 hr for caspases 3+7 quantification by fluorometric assay, and immediately for clonogenic survival. RESULTS: AS caused a significant reduction in Bcl-2 expression in all cell lines. P53 expression was elevated following RT treatment in LNCaP and LNCaP-BST cells. P21 was increased by RT treatment in all cell lines. AS caused a significant increase in caspase 3+7 activity over the mismatch (MM) controls in all cell lines. When AS was combined with RT, caspase 3+7 activity was further increased significantly over all other groups in all cell lines. Moreover, AS+RT resulted in significantly reduced clonogenic survival over MM+RT, which was dampened in the Bcl-2 overexpressing lines. CONCLUSIONS: To our knowledge, these data demonstrate for the first time that a Bcl-2 specific AS oligonucleotide sensitizes prostate cancer cells to RT. p53 is not required for this effect.

Apoptosis↗
PubMed1997

Cell damage induced by Angiovist-370 and 308nm excimer laser radiation.

BACKGROUND AND OBJECTIVE: Radiographic contrast media containing iodine-labeled organic compounds can be present in the irradiated field during laser angioplasty using 308 nm excimer laser radiation. These compounds absorb light at 308 nm and may undergo photochemical reactions that produce products that damage cells. STUDY DESIGN/MATERIALS AND METHODS: This study was undertaken to determine whether photoproducts that damage human lymphocytes in vitro are formed when Angiovist 370 (AV), a contrast medium containing triiodinated aromatic compounds, is exposed to 308 nm radiation. RESULTS: The absorption spectrum of AV developed a new peak at 360 nm that extended to wavelengths greater than 500 nm when dilute AV solutions were exposed to 308 nm radiation indicating that photoproducts were formed. Irradiating dilute AV solutions above a layer of human lymphocytes caused a dose-dependent decrease in thymidine incorporation using fluence rates between 5.2 x 10(6) and 1.0 x 10(8) W/cm2. Decreased DNA synthesis was independent of the pulse length (10 ns vs. 230 ns) but was lower, at a given dose, when the highest fluence rate was used. Incubation of lymphocytes with preirradiated AV solutions also decreased incorporation of thymidine in a radiation dose-dependent manner. The cell damaging photoproducts in preirradiated AV solutions were unstable; within 15 min, the effectiveness had decreased by approximately 85%. CONCLUSIONS: These results indicate that exposure of AV to 308 nm excimer laser radiation produces photochemical products that damage human cells in vitro.

Angioplasty, Balloon, Laser-Assisted↗
PubMed2003

Gene therapy delivery of endostatin enhances the treatment efficacy of radiation.

BACKGROUND AND PURPOSE: To evaluate whether sustained expression of mouse endostatin by adeno-associated virus (AAV)-mediated gene transfer can enhance the treatment efficacy of ionizing radiation. MATERIALS AND METHODS: Mouse endostatin was cloned into recombinant AAV (rAAV) under the control of CMV beta-actin promoter. Recombinant mouse endostatin expressed via AAV gene transfer was tested for biological activity in endothelial cells. The impact of elevated serum levels of endostatin on tumor-induced angiogenesis was evaluated using an in vivo angiogenesis assay. The anti-tumor efficacy of combining rAAV-mediated endostatin delivery with radiation was evaluated in a human colorectal tumor model (HT29). RESULTS: Recombinant mouse endostatin expressed through an AAV vector (rAAV-mEndo) inhibited endothelial cell proliferation (by 40-45%) and migration (by 22-33%). Intramuscular injection of rAAV-mEndo (1x10(9) i.u.) led to a sustained serum endostatin level of approximately 500 ng/ml. Compared to control animals this endostatin level was sufficient to inhibit tumor cell-induced vessel formation (37 vs. 28.5, P<0.05) and delay the growth of HT29 xenografts (time from 200 to 1,000 mm(3), 21 vs. 34.5 days, P<0.05). When combined with ionizing radiation, elevated serum endostatin levels significantly enhanced the time for tumors to grow from 200 to 1,000 mm(3) (radiation, 34 days; endostatin plus radiation, 50 days, P<0.05). CONCLUSION: The delivery of endostatin via rAAV vectors may provide an effective means of enhancing the anti-tumor efficacy of radiation therapy.

Animals↗
PubMed2006

In vivo X-ray angiography in the mouse brain using synchrotron radiation.

BACKGROUND AND PURPOSE: We, for the first time, performed in vivo x-ray angiography in the mouse brain using SPring-8, a third-generation synchrotron radiation facility. METHODS: A thin PE-50 tube was placed in the unilateral external carotid artery in adult male C57BL/6J mice. While maintaining the blood flow in the internal carotid artery, 33 muL of contrast agent was injected and then selective angiography of the hemisphere was performed. RESULTS: The average diameters of cerebral artery were as follows: 142.5+/-7.90 microm in middle cerebral artery, 138.3+/-9.35 microm in anterior cerebral artery, 120.5+/-5.53 microm in posterior cerebral artery, and 162.6+/-10.87 microm in internal carotid artery (n=5). To demonstrate the changes in diameter, we induced hypercapnia and detected the dilatation of the vessels between 121% and 124% of the original diameters (n=5). We also repeated angiography in the mice before and after intracarotid injection of vasodilatation drugs papaverine hydrochloride, ATP disodium, and fasudil hydrochloride hydrate and demonstrated the chronological changes in the diameters in each artery at 1, 5, 15, and 30 minutes after injection (n=1 for each drug). CONCLUSIONS: Using only a minimum volume of the contrast agent, synchrotron radiation enables us to study x-ray angiography in the mouse brain. The morphology of the vessels can be clearly observed under physiological conditions. The diameters and their changes can also be successfully studied in vivo.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2025

Unraveling cellular dynamic changes in tumor evolution induced by long-term low dose-rate radiation.

BACKGROUND: In recent years, there has been a steady increase in professionals engaged in radioactive work. The biological impacts of long-term exposure to low dose-rate radiation remain elusive, as there is a dearth of systematic research in this field. METHODS: BEAS-2B cells were used to establish a cell model with continuous passaging after radiation exposure, which was subsequently subjected to in vivo tumorigenesis assays and in vitro malignant phenotype experiments. By scRNA-seq, we conducted copy number variation analysis, cell trajectory analysis, and cell communication analysis. Furthermore, we used FACS, molecular docking, multiplex immunohistochemistry, qRT-PCR, and co-immunoprecipitation to validate and further explore the molecular mechanisms driving tumor evolution. RESULTS: Long-term low dose-rate exposure is associated with a higher degree of malignancy, as evidenced by the induction of more CNV and EMT events, as well as the delayed activation of DNA repair pathways, which trigger increased genomic instability. The long-term low dose-rate specific ligand-receptor pair, ANGPTL4-SDC4, enhances cell malignancy by promoting angiogenesis in newly formed lung tumor cells. CONCLUSIONS: This study not only provides the first evidence and mechanistic explanation that long-term low dose-rate radiation leads to increased cellular malignancy but also offers valuable theoretical insights into the dynamic processes of early tumor evolution in lung cancer within the realm of tumor biology.

Humans↗
PubMed1998

Effectiveness of eye drops protective against ultraviolet radiation.

BACKGROUND: To test the effectiveness of commercially available ultraviolet (UV)-protective eye drops (8-hydroxy-1-methylchinolinium methylsulphate) which are recommended for protection against both solar and artificial UV radiation. METHODS: The spectral transmission in the wavelength range from 250 to 500 nm was investigated in 1-nm steps using a high-resolution double monochromator with holographic gratings of 2,400 lines/mm and a 1,000-watt halogen lamp as light source. The transmission spectrum was measured for different values of the layer thickness. RESULTS: The transmission of a liquid layer of about 10 microns, which corresponds to the thickness of the human tear film, shows a cut-off at 290 nm with a transmission of about 25-50% at shorter wavelengths. For wavelengths longer than 290 nm the transmission is higher than 90%. The threshold time ratio for keratitis formation with and without eye drops is above 0.93 considering solar radiation on the earth's surface and above 0.65 considering radiation from arc-welding, respectively. DISCUSSION: The transmission spectrum of the eye drops under realistic conditions does not show a protective effect against solar UV radiation. However, there exists reduction of UVC radiation in the spectral range typical of artificial UV sources such as arc-welding. We cannot recommend the application of these eye drops as an UV-protective aid against eye damage by solar UV radiation.

Eye↗
PubMed2003

Mobilized endothelial progenitor cells by granulocyte-macrophage colony-stimulating factor accelerate reendothelialization and reduce vascular inflammation after intravascular radiation.

BACKGROUND: Endothelial progenitor cells (EPCs) play a pivotal role in repair and regeneration of damaged vessels. We investigated the role of mobilized EPCs in the healing process after intravascular radiation therapy. METHODS AND RESULTS: One iliac artery of hypercholesterolemic rabbits was subjected to balloon injury and intravascular radiation with a Re-188 balloon and the contralateral iliac artery to balloon injury only. Rabbits received granulocyte-macrophage colony-stimulating factor (recombinant human GM-CSF) (60 microg/d subcutaneously) daily for 1 week, either 7 days before the angioplasty or at the time of angioplasty. Control rabbits received human albumin. GM-CSF significantly increased the double-positive (CD31+ and KDR+) fraction in peripheral blood monocytes and showed a higher number of EPCs than albumin after culture and, furthermore, enhanced migration and incorporation of EPCs. In the albumin group, intravascular radiation therapy reduced neointimal hyperplasia but delayed reendothelialization and aggravated monocyte infiltration. GM-CSF treatment significantly accelerated the reendothelialization and inhibited monocyte infiltration (reendothelialization index, 81+/-13% in the GM-CSF radiation [n=7] versus 30+/-11% in the control radiation [n=9] at 2 weeks, P<0.01). GM-CSF treatment produced an additional significant reduction in neointimal formation at 14 and 28 days after injury in the intravascular radiation groups (intima to media ratio, 0.14+/-0.11 in the GM-CSF radiation [n=5] versus 0.36+/-0.07 in the control radiation [n=5] at 4 weeks, P<0.01). CONCLUSIONS: GM-CSF treatment mobilizes EPCs, accelerates reendothelialization, and reduces monocytes infiltration after intravascular radiation therapy, suggesting that stem cell mobilization is a promising strategy for enhancing the vascular healing process after cytotoxic angioplasty.

Animals↗
PubMed2006

Integral radiation dose to normal structures with conformal external beam radiation.

BACKGROUND: This study was designed to evaluate the integral dose (ID) received by normal tissue from intensity-modulated radiotherapy (IMRT) for prostate cancer. METHODS AND MATERIALS: Twenty-five radiation treatment plans including IMRT using a conventional linac with both 6 MV (6MV-IMRT) and 20 MV (20MV-IMRT), as well as three-dimensional conformal radiotherapy (3DCRT) using 6 MV (6MV-3DCRT) and 20 MV (20MV-3DCRT) and IMRT using tomotherapy (6MV) (Tomo-IMRT), were created for 5 patients with localized prostate cancer. The ID (mean dose x tissue volume) received by normal tissue (NTID) was calculated from dose-volume histograms. RESULTS: The 6MV-IMRT resulted in 5.0% lower NTID than 6MV-3DCRT; 20 MV beam plans resulted in 7.7%-11.2% lower NTID than 6MV-3DCRT. Tomo-IMRT NTID was comparable to 6MV-IMRT. Compared with 6MV-3DCRT, 6MV-IMRT reduced IDs to the rectal wall and penile bulb by 6.1% and 2.7%, respectively. Tomo-IMRT further reduced these IDs by 11.9% and 16.5%, respectively. The 20 MV did not reduce IDs to those structures. CONCLUSIONS: The difference in NTID between 3DCRT and IMRT is small. The 20 MV plans somewhat reduced NTID compared with 6 MV plans. The advantage of tomotherapy over conventional IMRT and 3DCRT for localized prostate cancer was demonstrated in regard to dose sparing of rectal wall and penile bulb while slightly decreasing NTID as compared with 6MV-3DCRT.

Humans↗
PubMed2002

Influence of the leaf extract of Mentha arvensis Linn. (mint) on the survival of mice exposed to different doses of gamma radiation.

BACKGROUND: The aim of the present study was to evaluate the radioprotective effect of Mentha arvensis (mint) on the survival of mice exposed to various doses of whole-body gamma radiation. MATERIAL AND METHODS: The radioprotective effect of various doses (0, 2.5, 5, 10, 20, 40 and 80 mg/kg body weight) of chloroform extract of mint (Mentha arvensis Linn.) was studied in mice exposed to 10 Gy gamma radiation. RESULTS: The 10 mg/kg of mint extract was found to afford best protection as evidenced by the highest number of survivors in this group at 30 days post-irradiation, and further experiments were carried out using this dose of mint extract. The mice treated with 10 mg/kg body weight mint extract or oil were exposed to 6, 7, 8, 9 and 10 Gy of gamma radiation and observed for the induction of radiation-sickness and mortality up to 30 days post-irradiation. The mint extract pretreatment was found to reduce the severity of symptoms of radiation sickness and mortality at all exposure doses and a significant increase in the animal survival was observed when compared with the oil + irradiation group. All of the animals that were treated with 10 mg/kg mint extract and then exposed to 7 Gy irradiation were protected against the radiation-induced mortality when compared with the concurrent oil + irradiation group, in which 20% animals died by 30 days post-irradiation. The mint extract treatment protected the mice against the gastrointestinal death as well as bone marrow deaths. The DRF was found to be 1.2. The drug was non-toxic up to a dose of 1,000 mg/kg body weight, the highest drug dose that could be tested for acute toxicity. CONCLUSION: From our study it is clear that mint extract provides protection against the radiation-induced sickness and mortality and the optimum protective dose of 10 mg/kg is safe from the point of drug-induced toxicity.

Animals↗
PubMedDate not supplied

Caspase-1 enhances the apoptotic response of prostate cancer cells to ionizing radiation.

BACKGROUND: The significance of caspase-1 in prostate cancer has recently been documented (Cancer Res 61: 1227-1232, 2001). In this study, we investigated the role of caspase-1 in radiation-induced apoptosis in order to identify the significance of this apoptotic initiator in radiation resistance. MATERIALS AND METHODS: Caspase-1 was over-expressed in DU-145 prostate cancer cells (which have weak endogenous expression of caspase-1), via transfection-mediated gene transfer. Stable transfectants were cloned and expression of caspase-1 was established at the mRNA and protein levels by RT-PCR and Western blot, respectively. Caspase-1 overexpressing clones were characterized for their apoptotic response to ionizing irradiation (0-9 Gy) on the basis of cell viability and Hoechst staining assays and profiling of expression of key apoptosis regulators, such as caspase -3 and -9. RESULTS: Caspase-1 transfectants exhibited a greater sensitivity in response to ionizing radiation than the neomycin control transfectants, as demonstrated by a dramatic loss in cell viability, that temporally correlated with apoptosis induction. Furthermore, caspase-1 overexpression resulted in a significant decrease in clonogenic survival following treatment with ionizing radiation, while the caspase-1 inhibitor, Z-YVAD.fmk, suppressed apoptosis induction in caspase-1 transfectants (p<0.008). The apoptotic effect was associated with increased expression of the pro-enzyme form of caspase-3 in both the caspase-1 transfectants and neo controls cells, with the activated caspase-3 being detected in caspase-1 transfectants only. While this activation of caspase-3 was paralleled by an elevated caspase-9 expression at 9 h post-irradiation, there was no major induction in Apaf-1 or cytochrome c release. CONCLUSION: The present study provides an initial mechanistic insight into the functional involvement of caspase-1 in changing the apoptotic threshold of prostate cancer cells to radiation. These findings will enhance the understanding of the molecular basis of prostate tumor radioresistance and may have significant clinical relevance in improving the therapeutic index of radiotherapy in prostate cancer patients.

Apoptosis↗
PubMedDate not supplied

In vitro combined modality treatment of prostate carcinoma cells with 17-(allylamino)-17-demethoxygeldanamycin and ionizing radiation.

BACKGROUND: The effect of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), a benzoquinone-ansamycin-type Hsp90-inhibitor, on the expression of focal adhesion kinase (FAK) and, when combined with ionizing radiation, on the clonogenicity of prostate cancer cells were determined. MATERIALS AND METHODS: FAK was analyzed by Western immunoblot. Prostate carcinoma cells were exposed either to 17-AAG alone or combined with a single radiation fraction of 3 Gy. RESULTS: FAK concentrations were reduced by 17-AAG in a time-dependent manner. Treatment with 100 nM 17-AAG for 24 h reduced clonogenicity by 90%. The plot of surviving fraction versus radiation energy dose yielded roughly parallel graphs for solvent- and 17-AAG-treated cells. CONCLUSION: 17-AAG induced rapid degradation of FAK A single radiation fraction of 3 Gy did not enhance the dose-dependent drug-effect on survival. In this sequence, the combined effect of both modalities towards clonogenicity was largely additive.

Benzoquinones↗
PubMed2002

[MnSOD gene regulated by aminopeptidase N promoter specifically protects bone marrow from radiation].

BACKGROUND & OBJECTIVE: It is an effective way to induce radio-tolerant gene into hematopoietic cells in bone marrow for overcoming the suppression of radiotherapy on hematopoietic system. However, this also increases the radiation tolerance of tumor cells. This study was designed to investigate a method to specifically protect bone marrow cell from being damaged by radiation, along without increasing resistance of tumor cell to radiation. METHODS: The retrovirus vector of manganese superoxide dismutase (MnSOD) gene regulated by aminopeptidase N (APN) bone marrow-specific gene promoter was constructed and induced into myeloblastic KG1a and cancer cell BEL7402. MnSOD mRNA level was analyzed by PT-PCR; MnSOD activity in the cells was determined; the sensitivity of bone marrow cell and hepatic carcinoma cell to x-ray was detected by cell survival test; the cell apoptosis was analyzed with flow cytometry and fractural DNA electrophoresis. RESULTS: The MnSOD mRNA level and enzyme activity in KG1a cells transferred with the gene was obviously increased. Expression of MnSOD mRNA drove by APN myelo-specific promoter effectively inhibited apoptosis of KG1a cells induced by radiation and endowed KG1a cell line with the enhancement of tolerance to radiation, which increased by 3.7 folds compared to parental cells at the dose of 10 Gy. In contrast, the level of MnSOD mRNA, the enyme activity of MnSOD and the radiosensitivity had no significant change in BEL 7402 cells transduced with MnSOD gene. CONCLUSION: APN bone marrow-specific promoter could control MnSOD gene expression highly in myeloid cell and lower in cancer cell. In the process of killing of cancer cell by x-ray, MnSOD gene regulated by APN bone marrow-specific promoter could specifically protect myeloid cell. This study provides a new clue to solve the bone marrow suppression in high dose radiotherapy.

3T3 Cells↗