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Biomedical subjects

A Han

Publications and source records attributed to A Han.

At least 55 records · Page 3Linked to original sources
PubMed1984

Multifractionation of 60Co gamma-rays reduces neoplastic transformation in vitro.

Incidences of neoplastic transformation of 10T 1/2 cells, derived from a C3H mouse embryo, were measured following irradiation of cells with 60Co gamma-rays delivered in single total doses, from 25 to 300 rads, or in different numbers of fractions and with different time intervals between fractions. Throughout the range of total doses that was examined (25-300 rads) exposure of asynchronous, actively growing 10T 1/2 cells to a dose of gamma-rays in five equal daily fractions, rather than in a single exposure, results in a significant reduction in transformation frequency. The initial part of the induction curve fits a straight line quite well. The slope of the line for five daily fractions is approximately 3-fold less steep than that for single exposures. A further increase in the interfraction interval, to 48 h, or further reductions in the dose per fraction, led to additional decreases in the incidence of neoplastic transformation. Our observations are consistent with a net 'error-free' repair of subtransformation damage as a result of protracted irradiation with 60Co gamma-rays.

Animals↗
PubMed1984

Accumulation of unesterified arachidonic acid in ischemic canine myocardium. Relationship to a phosphatidylcholine deacylation-reacylation cycle and the depletion of membrane phospholipids.

Studies in ischemic canine left ventricle have shown that the depletion of membrane phospholipids is a critical event in the development of a sarcolemmal calcium permeability defect and associated irreversible myocyte injury. The mechanism of phospholipid loss is unclear, but may be due to the activation of endogenous phospholipases. Since arachidonic acid is a fatty acid found almost entirely in phospholipid, increases in arachidonate provide evidence for increased phospholipase activity. The present study was designed to examine the temporal relationship of the accumulation of free arachidonate with the onset of phospholipid depletion during fixed ligation of the left anterior descending coronary artery in canine myocardium. The following results were demonstrated in ischemic canine myocardium: (1) the accumulation of unesterified arachidonate is minimal during 10-30 minutes of ischemia, but is significantly increased after prolonging the duration of ischemia to 1-3 hours; (2) significant increases in arachidonate precede the development of a significant decrease in total phospholipid content; (3) the decrease in the arachidonate content of phosphatidylcholine is accompanied by similar decreases in all of the fatty acyl moieties; (4) the arachidonate content of lysophosphatidylcholine and diacylglycerol are unchanged during myocardial ischemia; (5) there is evidence of a deacylation-reacylation cycle in phosphatidylcholine prior to the accumulation of free arachidonate; (6) the fatty acyl specificity of the lysophosphatidylcholine acyltransferase corresponds to the pattern of fatty acyl remodeling of phosphatidylcholine during early myocardial ischemia. These data suggest that the accumulation of arachidonate may be a more sensitive measure of phospholipid degradation than the decrease in total phospholipid content in ischemic canine myocardium. It is postulated that the defective reacylation of arachidonate into phosphatidylcholine may contribute to the net loss of membrane phospholipid during myocardial ischemia.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1984

Repair processes and radiation quality in neoplastic transformation of mammalian cells.

Appropriate in vitro mammalian cell systems facilitate the study of cellular mechanisms of radiation oncogenesis. C3H 10T1/2 cells derived from mouse embryo have been used to study the effects of protracted irradiation on cell killing and incidence of neoplastic transformation. Neoplastic transformation in these cells results in the appearance of colonies of densely piled up, disorganized cells that grow on top of the contact inhibited monolayer of nontransformed cells. Protracted exposures of 60Co gamma rays or fission-spectrum neutrons (from the JANUS reactor at the Argonne National Laboratory) were given either at low dose rates or as multifractionated regimens using high dose rates. Dose protraction of gamma rays by multifractionation at a high dose rate (50 rad/min) results in appreciable reduction in cell killing and also significantly reduces the incidence of neoplastic transformation. Irradiation at a low dose rate has the same qualitative effect. In contrast, protracted exposures of fission-spectrum neutrons, given at a low dose rate (0.086 or 0.43 rad/min), result in significant enhancement of the frequency of transformation in the dose region of up to 80 rad. However, the survival of cells is essentially the same as that for the same single dose of neutrons given at a high dose rate. These observations are consistent with net "error-free" repair of transformational damage following protracted exposure of a low LET radiation and possibly a net "error-prone" repair of transformational damage after protracted irradiations with fission-spectrum neutrons.

Animals↗
PubMed1984

Mechanisms of recovery from sublethal damage and potentially lethal damage induced by BrdUrd/313 nm light treatment: alkali-labile lesions.

BrdUrd pulse labelling of synchronous Chinese hamster cell cultures was used to correlate repair of sublethal damage with removal of alkali-labile lesions. Both processes were modified in a quantitatively similar manner by cysteamine. In addition, the age responses for repair of sublethal damage and for cysteamine reduction of repair agreed. Through the use of thymidine as an S-phase-blocking agent it was further demonstrated that progression past the S-phase of the cell cycle was required for the loss of resistance to UVB light in BrdUrd-substituted cells. Similarly, a thymidine block administered before synthesis upon the BrdUrd-substituted template prevented the cell from acquiring the sensitivity to UVB light normally associated with synthesis on a lesioned template. The UVB-light-sensitive mutant V79-UC was shown to have reduced capacities both for the accumulation of sublethal injury and for the removal of alkali-labile lesions. These data support the notion that alkali-labile lesions are responsible for sublethal damage in BrdUrd pulse-labelled Chinese hamster cells.

Animals↗
PubMed1984

Repair of neoplastic transformation damage following protracted exposures to 60Co gamma-rays.

The incidences of neoplastic transformation induced by 60Co gamma-rays in exponentially growing mouse embryo 10T1/2 cells were measured following acute and protracted exposures. Delivery of 60Co gamma-rays at a low dose rate (0.1, 0.5, 2.5 cGy min-1) compared with a high dose rate (100 cGy min-1) results in appreciable, dose rate dependent reductions in cell killing and, independent of the effect on cell survival, reduces significantly the incidence of neoplastic transformation. Exposure of exponentially growing 10T 1/2 cells to a dose of gamma-rays in 5 equal daily fractions also significantly reduces transformation frequency, compared with delivery in a single dose, throughout the dose range examined (25-300 cGy). The initial parts of the induction curves are fitted quite well by a linear dose dependence. The slopes of the regression lines for multifractionation delivery or irradiation at 0.1 cGy min-1, are one-third and one-half, respectively, of those for single exposures at a high dose rate. Increasing the inter-fraction interval up to 48 h, or reduction of the dose per fraction further reduce incidence of neoplastic transformation. We conclude that protracted exposures of low LET radiation result in a net "error-free" repair of subtransformation damage.

Animals↗
PubMed1984

Possible error-prone repair of neoplastic transformation induced by fission-spectrum neutrons.

We have examined the effect of fission-spectrum neutrons from the JANUS reactor at Argonne National Laboratory, delivered either as acute or protracted irradiation, on the incidence of neoplastic transformation in the C3H 10T1/2 mouse embryo cell line. Acute exposures were delivered at 10-38 cGy min-1, protracted exposures at 0.086 or 0.43 cGy min-1. The total doses for both ranged from 2.4 to 350 cGy. In the low dose region (2.4-80 cGy), there was a large enhancement in transformation frequency when the neutrons were delivered at the low dose rates compared with the high dose rates, but the survival of the cells was not significantly different between the two exposures conditions. Analysis of the initial parts of the curves shows that the regression line for protracted doses is about 9 times steeper than that for single acute exposures. Finally, the possibility is discussed that an "error-prone" repair process may be causing the enhanced transformation frequency by protracted neutron exposures.

Animals↗
PubMed1983

Metabolism of corticosterone in the mouse. Identification of 11 beta, 20 alpha-dihydroxy-3-oxo-4-pregnen-21-oic acid as a major metabolite.

We have shown that mouse liver contains enzymes that catalyze the conversion of the ketol side chain to the 20-hydroxy-21-oic acid side chain. In this paper, we have studied the oxidative metabolism of corticosterone to acidic end products in intact mice. A significant fraction of radioactivity from intraperitoneal injections of [4-14C]corticosterone appeared in liver and intestine within 5 min. The major steroid in liver at 5 min postinjection was found to be corticosterone, although acidic metabolites were detected. Within 30 min after injection, 11 beta, 20 alpha-dihydroxy-3-oxo-preg-4-en-21-oic acid became the dominant steroid. At 60 min, it was the major steroid isolated from liver or intestine. Several other acid metabolites were present in lesser amounts in both organs. About half of the remaining radioactive metabolites in liver and intestine were steroid acids, as determined by their reaction with diazomethane. The identification of the major steroid acid as 11 beta, 20 alpha-dihydroxy-3-oxo-pregn-4-en-21-oic acid was made by comparing the chromatographic behavior of the free acid and its methyl ester with that of authentic synthetic acid using thin layer and high performance liquid chromatography. Identity was confirmed by showing that the specific activities of the homogeneous 14C-labeled free acid remained unchanged when reanalyzed as the 21-methyl ester.

Animals↗
PubMed1983

Suppressive action of near-ultraviolet light on ouabain resistance induced by far-ultraviolet light in Chinese hamster cells.

The interaction between ultraviolet light (UV-C) from germicidal lamps (254 nm) and near-ultraviolet light (UV-B) from Westinghouse Sun Lamps (290-345 nm) was studied in Chinese hamster V79 cells by measuring the effectiveness of combined exposures to induce the resistance to 6-thioguanine or to ouabain. Exposure of cells to a conditioning dose of UV-B (approximately 70% survival) results in significant inhibition of the induction by UV-C of cells resistant to ouabain. The inhibition is lost, however, if cells are incubated for 12 h at 37 degrees C between exposures. Inhibition is also observed when cells are preirradiated with a dose of UV-B filtered with polystyrene (300-345 nm) which, in itself, has no effect on cell killing. Conditioning exposures of unfiltered or filtered UV-B light do not inhibit the induction of 6-thioguanine-resistant cells by UV-C light, and the effects of UV-B and UV-C light are largely independent.

Animals↗
PubMed1983

Failure of steroid sulfatase to desulfate vitamin D3 sulfate.

Patients with recessive X-linked ichthyosis lack activity of the enzyme steroid sulfatase. One of the more striking clinical findings in these patients is the improvement in stratum corneum shedding in the summer. Since vitamin D is one steroid responsive to sunlight, we examined whether or not vitamin D3 sulfate is a substrate for steroid sulfatase. Enzyme preparations active against other sulfated steroids caused no desulfation of vitamin D3 sulfate.

Cholecalciferol↗
PubMed1983

In vivo esterification of a synthetic 125I-labeled fatty acid into cardiac glycerolipids.

Recent studies have demonstrated that fatty acids can be successfully utilized as myocardial imaging agents. 125I-paraphenylpentadecanoic acid (IPPA), a synthetic fatty acid, accumulates within the myocardium and can be visualized by conventional gamma scintigraphy. To determine if IPPA was incorporated into cardiac lipids in a pattern similar to palmitate, IPPA was purified by liquid chromatography, bound to fat-free albumin, and administered by intravenous injection to male Sprague-Dawley rats. After 2.5, 5, 10, and 30 min, the hearts were excised and the lipids were extracted in chloroform-methanol. The uptake of IPPA into the myocardium reached a maximal value after 2.5 min, and 95% of the 125I was found in the cardiac lipid fraction after chromatographic separation. Over 65% of the IPPA was found in cardiac triglycerides, whereas approximately 10% was present in membrane phospholipids (predominantly phosphatidylcholine and phosphatidylethanolamine). This pattern of IPPA incorporation is similar to that reported for intravenously administered [3H]palmitate. The rate of turnover of IPPA present in the triglyceride fraction was threefold faster than the rate of the IPPA which was incorporated into membrane lipids. At all time periods examined, the methanol-water soluble end products of IPPA oxidation did not account for more than 5% of the total IPPA present within the myocardium. The present study indicates that IPPA is incorporated primarily into triglycerides and other cardiac lipids in a pattern similar to palmitate.

Animals↗
PubMed1982

Enhanced transformation of mouse 10T1/2 cells by 12-O-tetradecanoylphorbol-13-acetate following exposure to X-rays or to fission-spectrum neutrons.

Addition of the tumor promoter of 12-O-tetradecanoylphorbol-13-acetate (TPA) to C3H/10T1/2 cells after exposure to either X-rays or to fission-spectrum neutrons increases significantly the frequency of transformation without any effect on cell survival. However, treatment of unirradiated cells with 0.1 micrograms of TPA per ml alone results in a small increase in transformation frequency above background (i.e., from 1.1 x 10(-5) to 1.0 x 10(-4). Thus, besides being a promoter, TPA is also a weak initiator. Enhancement of radiation-induced transformation by TPA was relatively greater after low compared to high doses of either radiation. In addition, TPA causes the relative biological effectiveness of neutrons compared to X-rays to increase with increasing dose or with increasing frequency of transformation rather than to decrease, when TPA is not used. For X-ray doses from zero to approximately 120 rads, TPA raises transformation to frequencies approximately equal to those due to neutrons alone. Analysis of TPA enhancement in the context of the combined effect of two inducing agents, i.e., TPA plus a radiation, indicates that with either radiation TPA acts synergistically. Lastly, TPA was found to alter the dependence of transformation frequency on the density of viable cells. As opposed to a constant frequency of transformants per surviving (or viable) cell, which we observed after a fixed dose of X-rays or neutrons for a range of cell inocula, the addition of TPA increased the frequency of transformation for cell inocula (i.e., from approximately 20 to 6000 viable cells per 90-mm Petri dish). However, the frequency of transformation decreases with increasing size of the inoculum, a result that we interpret to indicate the combined effect of an interference with cell-to-cell communication by TPA plus the fading of initiation events due to the radiation.

Animals↗
PubMed1981

Spectral dependencies of killing, mutation, and transformation in mammalian cells and their relevance to hazards caused by solar ultraviolet radiation.

Using germicidal lamps and Westinghouse sunlamps with and without filtration, the effectiveness of ultraviolet and near-ultraviolet light in inducing molecular and cellular changes was measured. Cell survival and the induction of resistance to 6-thioguanine or to ouabain were measured with V79 Chinese hamster cells, cell survival and neoplastic transformation were measured with C3H mouse 10 T 1/2 cells, and the induction of pyrimidine dimers containing thymine was measured in both cell lines. The short-wavelength cutoff of the sunlamp emission was shifted from approximately 290 nm (unfiltered) to approximately 300 and approximately 310 nm by appropriate filters. Although it was found that the efficiency with which all end points were induced progressively decreased as the short-wavelength cutoff was shifted to longer wavelengths, the rates of decrease differed appreciably. For example, doses of near-ultraviolet light longer than approximately 300 nm that were effective in mutating or in transforming cells were ineffective in killing them. In respect to pyrimidine dimer induction, several but not all cellular end points were induced by dose ratios of sunlamp light (short-wavelength cutoff, approximately 290 nm) to germicidal lamp light (254 nm) in fairly close accord with the doses required to produce equivalent proportions of dimers. However, for near-ultraviolet light having cutoffs at longer wavelengths, the biological action observed was appreciably greater than what would be predicted from the proportion of dimers induced. From the latter observation, it is inferred that increasing intensities of short-wavelength ultraviolet light, as would be expected from reductions in stratospheric ozone around the earth, would result in smaller increases in biological action, e.g., skin cancer, compared to current levels of action than would be predicted from an action spectrum completely corresponding to that of a pyrimidine dimer induction spectrum in DNA.

Animals↗
PubMed1980

Repair of cell killing and neoplastic transformation at reduced dose rates of 60Co gamma-rays.

Using the C3H/10T1/2 mouse embryo-derived cell line, we measured the survival and incidence of neoplastic transformation following exposures of the cells to 60Co gamma-rays at an acute (100 rads/min) and at reduced (2.5, 0.5, and 0.1 rad/min) dose rates. Typical of what is generally observed with mammalian cells, at reduced dose rates, the survival of 10T1/2 cells increases as the dose rate is decreased due to the repair of sublethal damage during irradiation. The induction curve following acute exposures of 60Co gamma-rays is similar to that previously reported for 50-kV X-rays; the frequency initially rises rapidly, reaching a plateau of about 3 X 10(-3) transformants/survivor. The transformation induction curves for the reduced dose rates, while similar in shape to that for the high dose rate, exhibit a strong dependence on dose rate. All of the induction frequencies for reduced dose rates lie below those for 100 rads/min. In the low-dose region (i.e., 0 to 150 rads), our results are most extensive at 100 and at 0.1 rad/min. While each set of data in the low-dose region is fitted quite well by a linear dose dependence, the slope of the regression line at 0.1 rad/min is about one-half of that at 100 rads/min. We conclude that subeffective transformation damage, as well as sublethal damage, is repaired during low-dose-rate irradiation.

Animals↗