Biomedical subjects

T C Yang

Publications and source records attributed to T C Yang.

At least 55 records · Page 3Linked to original sources

PubMed1996

Radiogenic transformation of human mammary epithelial cells in vitro.

Cancer induction by space radiations is a major concern for manned space exploration. Accurate assessment of radiation risk at low doses requires basic understanding of mechanism(s) of radiation carcinogenesis. For determining the oncogenic effects of ionizing radiation in human epithelial cells, we transformed a mammary epithelial cell line (185B5), which was immortalized by benzo(a)pyrene, with energetic heavy ions and obtained several transformed clones. These transformed cells showed growth properties on Matrigel similar to human mammary tumor cells. To better understand the mechanisms of radiogenic transformation of human cells, we systematically examined the alterations in chromosomes and cancer genes. Among 16 autosomes examined for translocations, by using fluorescence in situ hybridization (FISH) technique, chromosomes 3, 12, 13, 15, 16, and 18 appeared to be normal in transformed cells. Chromosomes 1, 4, 6, 8, and 17 in transformed cells, however, showed patterns different from those in nontransformed cells. Southern blot analyses indicated no detectable alterations in myc, ras, Rb, or p53 genes. Further studies of chromosome 17 by using in situ hybridization with unique sequence p53 gene probe and a centromere probe showed no loss of p53 gene in transformed cells. Experimental results from cell fusion studies indicated that the transforming gene(s) is recessive. The role of genomic instability and tumor suppressor gene(s) in radiogenic transformation of human breast cells remains to be identified.

Breast↗

PubMed1996

Radiation-induced chromosomal instability in human mammary epithelial cells.

Karyotypes of human cells surviving X- and alpha-irradiation have been studied. Human mammary epithelial cells of the immortal, non-tumorigenic cell line H184B5 F5-1 M/10 were irradiated and surviving clones isolated and expanded in culture. Cytogenetic analysis was performed using dedicated software with an image analyzer. We have found that both high- and low-LET radiation induced chromosomal instability in long-term cultures, but with different characteristics. Complex chromosomal rearrangements were observed after X-rays, while chromosome loss predominated after alpha-particles. Deletions were observed in both cases. In clones derived from cells exposed to alpha-particles, some cells showed extensive chromosome breaking and double minutes. Genomic instability was correlated to delayed reproductive death and neoplastic transformation. These results indicate that chromosomal instability is a radiation-quality-dependent effect which could determine late genetic effects, and should therefore be carefully considered in the evaluation of risk for space missions.

Alpha Particles↗

PubMed1996

DNA damage and repair in oncogenic transformation by heavy ion radiation.

Energetic heavy ions are present in galactic cosmic rays and solar particle events. One of the most important late effects in risk assessment is carcinogenesis. We have studied the carcinogenic effects of heavy ions at the cellular and molecular levels and have obtained quantitative data on dose-response curves and on the repair of oncogenic lesions for heavy particles with various charges and energies. Studies with repair inhibitors and restriction endonucleases indicated that for oncogenic transformation DNA is the primary target. Results from heavy ion experiments showed that the cross section increased with LET and reached a maximum value of about 0.02 micrometer2 at about 500 keV/micrometer. This limited size of cross section suggests that only a fraction of cellular genomic DNA is important in radiogenic transformation. Free radical scavengers, such as DMSO, do not give any effect on induction of oncogenic transformation by 600 MeV/u iron particles, suggesting most oncogenic damage induced by high-LET heavy ions is through direct action. Repair studies with stationary phase cells showed that the amount of reparable oncogenic lesions decreased with an increase of LET and that heavy ions with LET greater than 200 keV/micrometer produced only irreparable oncogenic damage. An enhancement effect for oncogenic transformation was observed in cells irradiated by low-dose-rate argon ions (400 MeV/u; 120 keV/micrometer). Chromosomal aberrations, such as translocation and deletion, but not sister chromatid exchange, are essential for heavy-ion-induced oncogenic transformation. The basic mechanism(s) of misrepair of DNA damage, which form oncogenic lesions, is unknown.

Animals↗

PubMed1996

Biological dosimetry by interphase chromosome painting.

Both fluorescence in situ hybridization of metaphase spreads with whole-chromosome probes and premature chromosome condensation in interphase nuclei have been used in the past to estimate the radiation dose to lymphocytes. We combined these techniques to evaluate the feasibility of using painted interphase chromosomes for biodosimetry. Human peripheral lymphocytes were exposed to gamma rays and fused to mitotic Chinese hamster cells either immediately after irradiation or after 8 h incubation at 37 degrees C. Interphase or metaphase human chromosomes were hybridized with a composite probe specific for human chromosomes 3 and 4. The dose-response curve for fragment induction immediately after irradiation was linear; these results reflected breakage frequency in the total genome in terms of DNA content per chromosome. At 8 h after irradiation, the dose-response curve for chromosome interchanges, the prevalent aberration in interphase chromosomes, was linear-quadratic and similar to that observed for metaphase chromosomes. These results suggest that painting prematurely condensed chromosomes can be useful for biological dosimetry when blood samples are available shortly after the exposure, or when interphase cells are to be scored instead of mitotic cells.

Animals↗

PubMed1996

Rejoining and misrejoining of radiation-induced chromatin breaks. I. experiments with human lymphocytes.

Fluorescence in situ hybridization with a composite probe for human chromosome 4 and a probe that stained all centromeres was used to study gamma-ray induced breakage, rejoining and misrejoining in prematurely condensed chromosomes in human lymphocytes. Dose-response curves for the induction of all types of aberrations in prematurely condensed human chromosomes 4 were determined immediately after irradiation and after 8 h postirradiation incubation. In addition, aberrations were measured after various incubation times from 0 to 18 h after a dose of 7 Gy. Unrejoined chromosome breaks were the most frequent type of aberration observed immediately after irradiation. Approximately 15% of total aberrations observed were chromosome exchanges. After 8 h postirradiation incubation, the frequency of breaks in prematurely condensed chromosomes declined to about 20% of the initial value, and chromosomal exchanges became the most frequent aberration. Results of metaphase analysis were similar to those for prematurely condensed chromosomes after 8 h incubation with the exception that a significantly lower frequency of fragments was observed. Symmetrical and asymmetrical interchanges were found at similar frequencies at all doses. No complex exchanges were observed in lymphocyte chromosomes immediately after exposure. They accounted for about 1% of total exchanges in metaphase chromosomes at doses <3 Gy and about 14% at 7 Gy. Incomplete exchanges amounted to approximately 15% of total exchanges at all doses. The kinetics of break rejoining was exponential, and the frequency of exchanges increased with kinetics similar to that observed for the rejoining of the breaks. This increase in the total exchanges as a function of the time between irradiation and fusion was due to a rapid increase in reciprocal interchanges, and a slower increase in complex exchanges; the frequency of incomplete exchanges increased initially, then decreased with prolonged incubation to the level observed in metaphase. It is concluded that the formation of each kind of chromosome aberrations follows different kinetics.

Cells, Cultured↗

PubMed1996

Rejoining and misrejoining of radiation-induced chromatin breaks. II. Biophysical Model.

A biophysical model for the kinetics of the formation of radiation-induced chromosome aberrations is developed to account for the recent experimental results obtained with a combination of the premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) techniques. In this model, we consider the broken ends of DNA double-strand breaks (DSBs) to be reactant and make use of the interaction distance hypothesis. The repair/misrepair process between broken ends is suggested to consist of two steps; the first step represents the two break ends approaching each other, and the second step represents the enzymatic processes leading to DNA end-to-end rejoining. Only the second step is reflected in the kinetics observed in experiments using PCC. The model appears to be able to fit existing data for human cells. It is shown that the kinetics of the formation of chromosome aberrations can be explained by a single rate that characterizes both rejoining and misrejoining of DSBs, suggesting that repair and misrepair share the same mechanism. Fast repair (completed in minutes) in a subset of DSBs is suggested as an explanation of the complete exchanges observed with PCC in human lymphocytes immediately after irradiation. The fast repair component seems to be absent in human fibroblasts.

Cell Line↗

PubMed1995

Effects of alpha-particles on survival and chromosomal aberrations in human mammary epithelial cells.

We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of alpha-particles emitted from radon daughters, we concentrated our studies on the efficiency of alpha-particles. Confluent cultures of M/10 cells were exposed to accelerated alpha-particles [beam energy incident at the cell monolayer = 3.85 MeV, incident linear energy transfer (LET) in cell = 109 keV/microns] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for alpha-particles (D0 = 0.73 +/- 0.04 Gy), while a shoulder was observed for x-rays (alpha/beta = 2.9 Gy; D0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET alpha-particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for alpha-particles and linearquadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha Particles↗

PubMed1995

Radiogenic cell transformation and carcinogenesis.

Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic mechanism(s) of radiogenic transformation of human epithelial cells.

Animals↗

PubMed1994

Charged-particle mutagenesis II. Mutagenic effects of high energy charged particles in normal human fibroblasts.

The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 micrometer2 and 0.09 to 5.56 x 10(-3) micrometer2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(-5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

Cell Death↗

PubMed1994

Mutagenic effects of heavy ion radiation in plants.

Genetic and developmental effects of heavy ions in maize and rice were investigated. Heavy particles with various charges and energies were accelerated at the BEVALAC. The frequency of occurrence of white-yellow stripes on leaves of plants developed from irradiated maize seeds increased linearly with dose, and high-LET heavy charged particles, e.g., neon, argon, and iron, were 2-12 times as effective as gamma rays in inducing this type of mutation. The effectiveness of high-LET heavy ion in (1) inhibiting rice seedling growth, (2) reducing plant fertility, (3) inducing chromosome aberration and micronuclei in root tip cells and pollen mother cells of the first generation plants developed from exposed seeds, and (4) inducing mutation in the second generation, were greater than that of low-LET gamma rays. All effects observed were dose-dependent; however, there appeared to be an optimal range of doses for inducing certain types of mutation, for example, for argon ions (400 MeV/u) at 90-100 Gy, several valuable mutant lines with favorable characters, such as semidwarf, early maturity and high yield ability, were obtained. Experimental results suggest that the potential application of heavy ions in crop improvement is promising. RFLP analysis of two semidwarf mutants induced by argon particles revealed that large DNA alterations might be involved in these mutants.

Argon↗

PubMed1994

Postmortem chorionic villus sampling for cytogenetic evaluation of early fetal loss: a simple reliable method.

BACKGROUND: Early fetal losses associated with chromosome abnormalities produce most spontaneous abortions. It is not feasible to conduct cytogenetic studies with tissue culture postmortem because of tissue maceration and autolysis. METHODS: A total of 30 specimens from early fetal losses were karyotyped for chromosomal study. Success rate of the culture method is evaluated and compared. RESULTS: The abnormal karyotype rate was 33.3%. It was found that chorionic villus tissues had a higher culture rate than tests of fetal skin, amnion or amniocyte by early amniocentesis. CONCLUSIONS: Postmortem chorionic villus sampling at the time of diagnosis of early fetal death appears to offer the best, most simple and reliable method for obtaining a cytogenetic result, and also a good method for training residents in the chorionic villus sampling technique.

Adult↗

PubMed1993

Postoperative pain relief: lumbar and thoracic epidural morphine in thoracotomy.

Twenty-two patients undergoing thoracotomy were enrolled in a controlled, randomized trial to compare the effects of thoracic (group T) or lumbar (group L) epidural morphine in relieving postoperative pain. Epidural morphine was given as the patient first complained of pain in the recovery room. The effect of epidural morphine on pain relief was assessed by visual analogue scale and subjective grade. All patients were investigated 0, 10, 20, 30, 40, 50, 60, 75, 90, 105 and 120 minutes after a single bolus injection of epidural morphine. In assessment of pain relief by visual analogue scale, the difference between two groups was statistically significant (p < 0.05), evaluated 20, 30 and 40 minutes following treatment. There was no significant difference between two groups with regard to the effect of morphine as assessed by subjective grading. We concluded that thoracic epidural morphine took effect faster than lumbar epidural morphine. However, the effects of both kept similar since 50 minutes after morphine injection.

Adult↗

PubMed1993

Verification of endotracheal tube misplacement with the colorimetric carbon dioxide detector during anesthesia.

The sensitivity and reliability of the colorimetric end-tidal carbon dioxide detector (CETCO2) in verifying misplacement of endotracheal tube in the esophagus were assessed during induction of anesthesia using a conventional capnograph as control. Sixty patients of ASA physical status I and II undergoing elective minor surgery had their anesthesia induced with thiopental sodium (4-5 mg/kg, i.v.). Oral endotracheal intubation facilitated with succinylcholine (1.0 mg/kg, i.v.) was performed by junior residents. The time required for the appearance of discoloration from purple (< 2.5 torr) to tan-hued (3.8-7.6 torr) or yellow (> 15.2 torr) on the CETCO2 (T1) was significantly shorter (3.83 +/- 0.92 second vs. 8.23 +/- 1.14 second, p < 0.01) as compared with the initial display of the ETCO2 waveform on the capnograph (T2). Out of 60 patients esophageal intubation occurred in 6 (10%). Two patients had the color of the CETCO2 changing from purple to tan-hued at the first breath but reverting to purple at the 2nd or 3rd breath. Thus, the sensitivity of CETCO2 was 97.0% (3.0% false positive) if the first breath was chosen as the point of determination. However, if it was set at the 6th breath or yellow was chosen as the color of determination, the sensitivity increased to 100% without either false positive or false negative. In conclusion, the CETCO2 detector is reliable for the detection of correct placement of endotracheal tube during induction of anesthesia, no matter whether Jackson-Rees modification Ayre's T-piece or anesthetic breathing circuit is used for ventilation.

Adolescent↗

PubMed1992

Genetic changes in mammalian cells transformed by helium ions.

Midterm Syrian Hamster embryo (SHE) cells were employed to study high LET-radiation induced tumorigenesis. Normal SHE cells (secondary passage) were irradiated with accelerated helium ions at an incident energy of 22 MeV/u (9-10 keV/micrometer). Transformed clones were isolated after growth in soft agar of cells obtained from the foci of the initial monolayer plated postirradiation. To study the progression process of malignant transformation, the transformed clones were followed by monolayer subculturing for prolonged periods of time. Subsequently, neoplasia tests in nude mice were done. In this work, however, we have focused on karyotypic changes in the banding patterns of the chromosomes during the early part of the progressive process of cell transformation for helium ion-induced transformed cells.

Animals↗

PubMed1992

Charged-particle mutagenesis. 1. Cytotoxic and mutagenic effects of high-LET charged iron particles on human skin fibroblasts.

Cytotoxic and mutagenic effects of high-LET charged iron (56Fe) particles were measured quantitatively using primary cultures of human skin fibroblasts. Argon and lanthanum particles and gamma rays were used in comparative studies. The span of LETs selected was from 150 keV/microns (330 MeV/u) to 920 keV/microns (600 MeV/u). Mutations were scored at the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus using 6-thio-guanine (6-TG) for selection. Exposure to these high-LET charged particles resulted in exponential survival curves. Mutation induction, however, was fitted by the linear model. The relative biological effectiveness (RBE) for cell killing ranged from 3.7 to 1.3, while that for mutation induction ranged from 5.7 to 0.5. Both the RBE for cell killing and the RBE for mutagenesis decreased with increasing LET over the range of 1.50 to 920 keV/microns. The inactivation cross section (sigma i) and the action cross section for mutation induction (sigma m) ranged from 32.9 to 92.0 microns2 and 1.45 to 5.56 X 10(-3) microns2; the maximum values were obtained by 56Fe with an LET of 200 keV/microns. The mutagenicity (sigma m/sigma i) ranged from 2.05 to 7.99 X 10(-5) with an inverse relationship to LET.

Cell Survival↗

PubMed1991

Radiological health risks for exploratory class missions in space.

Crewmembers on missions to the Moon or Mars will be unavoidably exposed to ionizing radiation as they pass through the Van Allen belts and the Galactic Cosmic Ray (GCR) flux. There is the possibility for exposure to proton radiation from Solar Particle Events (SPE). Using absorbed doses and ICRP 26, Linear Energy Transfer (LET) -dependent quality factors, the following dose-equivalents are estimated: In a spacecraft with 0.75 cm aluminum walls (2 g/cm2) at solar minimum, the lunar round trip dose-equivalent is less than 0.05 Sv. During a Mars mission the estimated dose-equivalents are: outbound (Van Allen Belts) <0.02 Sv; Earth to Mars (205 days exposure to free space GCR) 0.32 Sv; 30 days on the Martian surface (GCR) 0.023 Sv; Mars to Earth (225 days exposure to free space) 0.35 Sv; and through the Van Allen Belts 0.02 Sv. Conventionally, the total of 0.73 Sv over 460 days could be expected to increase the risk of cancer mortality in a 35-year old male astronaut by about one percent. However three-fourths of the dose-equivalent in free space is contributed by high LET heavy ions (Z > or = 3) and target fragments with average quality factors of 10.3 and 20 respectively. The biological effectiveness of these radiations is poorly understood; so the quality factors are set at conservatively very high values. The entire concept of absorbed dose/quality factor/dose-equivalent as applied to GCR must be reconsidered.

Animals↗

PubMed1990

Response of cultured human airway epithelial cells to X-rays and energetic alpha-particles.

Radon and its progeny, which emit alpha-particles during decay, may play an important role in inducing human lung cancer. To gain a better understanding of the biological effects of alpha-particles in human lung we studied the response of cultured human airway epithelial cells to X-rays and monoenergetic helium ions. Our experimental results indicated that the radiation response of primary cultures was similar to that for airway epithelial cells that were transformed with a plasmid containing an origin-defective SV40 virus. The RBE for cell inactivation determined by the ratio of D0 for X-rays to that for 8 MeV helium ions was 1.8-2.2. The cross-section for helium ions, calculated from the D0 value, was about 24 microm 2 for cells of the primary culture. This cross-section is significantly smaller than the average geometric nuclear area (approximately 180 microms 2), suggesting that an average of 7.5 alpha-particles (8 MeV helium ions) per cell nucleus are needed to induce a lethal lesion.

Alpha Particles↗

PubMed1990

Plain film radiographic findings in lumbar disc protrusion: correlation with computed tomography iohexol myelography.

A retrospective study was devised to determine the correlation between plain film radiographic findings and computed tomography iohexol myelography in the recognition of lumbar disc protrusion. A group of 61 patients who had chronic low back pain seen in Taitung Mackay Memorial hospital from January 1, 1988 to December 31, 1988 was studied. In comparison of 207 lumbar disc protrusion, reaching an accuracy close to 80% but cannot distinguish between disc bulging or herniation. Spur formation correlated to a lesser extent. Subluxation of facet joints, discogenic sclerosis and vacuum phenomenon were all specific to disc protrusion; however, their rare occurrences have limited their usefulness in the recognition of disc protrusion.

Adult↗