REASSESSMENT OF THE DIFFERENTIAL EFFECTS OF ULTRAVIOLET AND IONIZING RADIATION ON HIV PROMOTER: THE USE OF CELL SURVIVAL AS THE BASIS FOR COMPARISONS

Abstract: Effects of different radiation treatments on the human immunodeficiency virus-1 (HIV) promoter were reassessed for exposures comparable to those encountered in clinical or cosmetic practice, using survival of the host cell as a basis for comparisons. The exposures were performed with two ultraviolet radiation sources commonly used as medical or cosmetic devices (UVASUN 2000 and FS20 lamps), a germicidal (G15T8) lamp and an X-ray machine. The UVC component of the FS20 lamp was filtered out. The emission spectra of the lamps were determined. The characteristics of these sources allowed us to discriminate among effects of UVA1 (340–400 nm), UVB + UVA2 (280–340 nm) and UVC (254 nm) radiations. Effects of irradiation were ascertained using cultures of HeLa cells stably transfected with the HIV promoter linked to a reporter—chloramphenicol acetyl transferase—gene. The exposures used caused at least two logs of cell killing. In this cytotoxicity range, UVA1 or X radiations had no effect on the HIV promoter, whereas UVB + UVA2 or UVC radiations activated the HIV promoter in a fluence-dependent manner. Survivals following exposure to UVB + UVA2 or UVC radiation were (1) at the lowest measurable HIV promoter activation, 30 and 20%, respectively, (2) at one-half maximal activation, 6 and 3%, respectively and (3) at the maximal activation, 0.5 and 0.2%, respectively. The results suggest that, among the radiations studied, UVB is the most important modality from the viewpoint of its potential effects on HIV-infected individuals, since (1) UVA1 or X radiations have no effects on the HIV promoter, (2) human exposure to UVC radiation is infrequent and (3) human UVB exposure is very common.     

Participation of an excited monomer in the propagation reaction of the γ-ray induced polymerization of ethylene

In the polymerization of ethylene, the reactivity of the growing radical produced by γ-radiation was compared with that of the radical from 2,2′-azobisisobutyronitrile. The radicals produced in the polymerization at around room temperature were long-lived irrespective of the method of initiation. However, it was found that the radical produced by γ-radiation became unreactive to ethylene when the reaction system was not exposed to γ-rays. Irradiation with γ-rays or ultraviolet light in a region below about 3900 Å was required for its chain growth. On the other hand, the radical from AIBN was always reactive, and the reactivity was little changed by γ-radiation or by the presence of a trace amount of radiolysis products of ethylene. In explaining of these characteristic differences between the nature of these radicals produced by two different methods of initiation, some other information on their reactivity was reviewed, and the participation of an excited ethylene in a dimer form was proposed, as for the propagation reaction of the γ-ray-induced polymerization.     

The role of retroviral dUTPases in replication and virulence

Several retroviruses, including equine infectious anemia virus (EIAV), visna virus, caprine arthritis-encephalitis virus (CAEV) and feline immunodeficiency virus (FIV) encode dUTPase. The role of this enzyme in the replication of these viruses has been scrutinized, with particular emphasis on potential roles for dUTPase in virulence and viral mutation rate. Overall, the results of these studies have indicated a central role for dUTPase in facilitating productive viral replication in non-dividing cells. The requirement for dUTPase in EIAV, which replicates exclusively in macrophages, may be the most stringent. Studies of dUTPase mutants of virulent EIAV clones suggest that the enzyme is a major determinant of virulence. In contrast, FIV readily replicates in dividing cell populations such as CD4+ and CD8+ T cells, and B cells as well as in non-dividing macrophages. Thus, the virus burden and disease sequelae are lowered in cats infected with a dUTPase-minus FIV relative to cats infected with wild type FIV, but not totally abrogated. Growth in macrophages is attenuated with the DU-minus FIV with evidence of a 5 to 8-fold increase in G-->A transition mutations in viral integrants present in macrophages. These findings are consistent with an increase in uracil misincorporation in the absence of dUTPase, resulting in transition mutations that cripple the virus. Effects on virus replication and disease production have also been noted for dUTPase-deleted CEAV and visna virus. While HIV and SIV do not encode dUTPase some reports suggest that other viral and host cell factors may substitute for its activity. Betaretroviruses also encode dUTPase and while several of these cause significant disease, the role of dUTPase in their replication and pathogenesis is currently unknown.     

Effects of γ-radiation on the thermal stability of cobalt oxides

Pure cobaltic oxide, prepared by thermal decomposition of pure basic cobalt carbonate in air at 500°C, was subjected to different doses of γ-radiation varying between 5 and 50 M rad. The influence of γ-radiation on the thermal decomposition of cobaltic oxide to cobaltous oxide and the re-oxidation of CoO to Co₃O₄ was studied using DTA, with a controlled rate of heating and cooling. The effects of γ-radiation on the specific surface area (S_BET) and oxidation character of Co₃O₄ were also investigated.The DTA investigation revealed that γ-radiation effectively decreased the thermal stability of cobaltic oxide to an extent proportional to the dose employed. The maximum decrease in the thermal stability of 60% was attained by exposing Co₃O₄ solid to 30 M rad. γ-Irradiation, however, exerted no detectable effect on the re-oxidation of CoO by O₂ to Co₃O₄.The S_BET measurements showed that the small dose (5 M rad) of γ-radiation effected a decrease of 15% in the surface area of Co₃O₄, the higher doses (10–50 M rad) caused a further slight decrease of 18% in its surface area.γ-Irradiation was found to decrease the oxidation character of Co₃O₄ to an extent proportional to the dose employed.The decrease in the thermal stability of Co₃O₄ due to radiation is explained in terms of the decrease in the oxidation character of cobaltic oxide observed after subjecting the solid to γ-radiation.     

Reversible addition-fragmentation chain transfer polymerization initiated with γ-radiation at ambient temperature: an overview

Using γ-radiation as initiation source at ambient temperatures (i.e. T≈20 °C) for reversible addition-fragmentation chain transfer (RAFT) polymerizations allows for the generation of narrowly distributed polymeric material with living characteristics. It is shown that the living characteristics effected by RAFT agent mediated bulk polymerizations using γ-irradiation are associated with a RAFT mechanism rather than with reversible termination processes. Furthermore, γ-radiation as initiation source for an appropriate RAFT agent/monomer system allows for effective radical storage and the generation of long-lived reaction intermediates at ambient temperatures.The current overview further demonstrates how the RAFT process together with γ-radiation as source of initiation can be employed to graft various monomers onto polypropylene surfaces in a controlled manner.     

γ-辐照对PLLA分子量及结晶形态的影响

以左旋聚乳酸(PLLA)为研究对象,以多官能团单体三烯丙基异氰酸酯(TAIC)为交联剂,采用反应挤出技术制备了PLLA-TAIC体系,并利用60Co-γ射线源,在较低辐照剂量(Dose≤25kGy)范围内,对所制备的聚合物进行了γ-辐照。研究了γ-辐照剂量、交联剂含量对PLLA分子量和结晶形态的影响。结果表明,在0~25kGy辐照剂量范围内,PLLA-TAIC的粘均分子量(-Mη)随γ-辐照剂量的增加呈现出先升高后降低的变化趋势,辐照剂量为10kGy、TAIC含量为3份时,PLLA的-Mη提高的幅度最大;随着辐照剂量的增加,原料PLLA形成的球晶尺寸有所增大;对于γ-辐照的PLLA-TAIC体系,随着TAIC含量的增加,PLLA的结晶能力有所下降。     

Effect of γ-radiation on radionuclide retention in compacted bentonite

Compacted bentonite is proposed as an engineered barrier in many concepts for disposal of high level nuclear waste. After the initial deposition however, the bentonite barrier will inevitably be exposed to ionizing radiation (mainly γ) under anoxic conditions. Because of this, the effects of γ-radiation on the apparent diffusivity values and sorption coefficients in bentonite for Cs⁺ and Co²⁺ were tested under different experimental conditions. Radiation induced effects on sorption were in general more noticeable for Co²⁺ than for Cs⁺, which generally showed no significant differences between irradiated and unirradiated clay samples. For Co²⁺ however, the sorption to irradiated MX80 was significantly lower than to the unirradiated clay samples regardless of the experimental conditions. This implies that γ-radiation may alter the surface characteristics contributing to surface complexation of Co²⁺. With the experimental conditions used, however, the effect of decreasing sorption was not large enough to be reflected on the obtained D_a values.     

Improvement of polyethylene by irradiation in artificial joints

The decrease in socket thickness of several total hip prostheses was measured on X-ray film. The following prostheses were compared: (1) SOM “28 mm metal head and an ultra-high-molecular-weight-polyethylene (UHMWPE) socket irradiated with 10⁸ rad of γ-radiation”, (2) T-28 “28 mm metal head and a UHMWPE socket not irradiated”, (3) Bioceram “28 mm alumina head and UHMWPE not irradiated” and (4) irradiated Bioceram “28 mm alumina head and UHMWPE socket irradiated with 10⁸ rad of γ-radiation”.The average steady state wear rate of SOM, T-28, Bioceram and irradiated Bioceram were 0.076, 0.247, 0.098 and 0.072 mm/year, respectively.The weight bearing portion of the irradiated socket presented a clearly-outlined and irregular pattern of about 0.1 μm thickness having a smooth ripple surface. The scratch and holding phenomenon characteristics of non-irradiated sockets was not observed at all.In our experimental tests using an IS sliding wear test machine, the wear measured as decrease of thickness was smallest at 10⁸ rad, although there was an increase in the coefficient of friction. Our experimental and clinical findings suggest that the best total hip prosthesis at present is one with an alumina head and a UHMWPE socket irradiated with 10⁸ rad of γ-radiation.     

Medical UV Exposures and HIV Activation

This paper presents the first attempt to evaluate the potential of clinical UV exposures to induce the human immunodeficiency (HIV) promoter and, thus, to upregulate HIV growth in those skin cells that are directly affected by the exposure. Using the data for HIV promoter activation in vitro, we computed UVB and psoralen plus UVA (PUVA) doses that produce 50% of the maximal promoter activation (AD₅₀). Then, using (a) literature data for UV transmittance in the human skin, (b) a composite action spectrum for HIV promoter and pyrimidine dimer induction by UVB and (c) an action spectrum for DNA synthesis inhibition by PUVA, we estimated the distribution of medical UVB and PUVA doses in the skin. This allowed us to estimate how deep into the skin the HIV-activating doses might penetrate in an initial and an advanced stage of UVB or PUVA therapy. Such analysis was done for normal type II skin and for single exposures. The results allow us to predict where in the skin the HIV promoter may be induced by selected small and large therapeutic UVB or PUVA doses. To accommodate changes in skin topography due to disease and UV therapy, our considerations would require further refinements. For UVB we found that, when the incident dose on the surface of the skin is 500 J/m² (290–320nm) (initial stage of the therapy), the dose producing 50% of the maximal HIV promoter activation (AD^UVB₅₀) is limited to the stratum corneum. However, with an incident dose of 5000 J/m² (an advanced stage of the therapy), AD^UVB₅₀ may be delivered as far as the living cells of the epidermis and even to some parts of the upper dermis. For PUVA we found that, when the incident UVA doses are 25 or 100 kJ/m² (320–400nm) (an initial and an advanced stage of therapy, respectively), and the 8-methoxypsoralen concentration in the blood is 0.1 μg/mL (the desired level), the combined doses to the mid epidermis (and some areas of the upper dermis) are well below the 50% HIV promoter-activating PUVA dose (AD^PUVA₅₀). Only under the worst scenario conditions, i. e. an exceptionally high drug concentration in the patient's tissues and localization of HIV in the nearest proximity to the skin surface, would the combined PUVA dose expected during photochemotherapy exceed AD^PUVA₅₀. These results suggest that the probability of HIV activation in the epidermis by direct mechanisms is higher for UVB than for PUVA treatment. However, complexities of the UV-inducible HIV activation and immunomodulatory phenomena are such that our results by themselves should not be taken as an indication that UVB therapy carries a higher risk than PUVA therapy when administered to HIV-infected patients.     

The effect of orientation on the radiation induced degradation of polymers

A study has been made of the effect of orientation on the oxidative degradation of poly(vinylchloride) (PVC), low density polyethylene (LDPE) and high density polyethylene (HDPE) under the influence of γ- and u.v.-radiation. The effect of drawing in PVC is to increase the rate of oxidative degradation; in LDPE and HDPE, this rate decreases (especially for HDPE) both under u.v. and γ-radiation.     

Radiation synthesis and magnetic properties of novel Co0.7Fe0.3/Chitosan compound nanoparticles for targeted drug carrier

Chitosan coated Co_0.7Fe_0.3 compound nanoparticles were successfully synthesized through a γ-radiation route in inverse microemulsion system. An observation of transmission electron microscope (TEM) showed that the diameter of these nanoparticles was about 50 nm with narrow size-distribution. Investigations of properties of nanoparticles were also conducted with fourier transform infrared spectrometer (FT-IR), X-ray diffraction (XRD) and energy dispersion spectrum (EDS). Analysis of vibrating sample magnetometer (VSM) indicated that the nanoparticles were superparamagnetic with a saturation magnetization of 24 emu/g. These compound nanoparticles were undertaken to allow for the magnetically targeted cancer.     

Effect of heat and solvent treatment on radiation grafting of acrylic acid to poly(ethylene terpehthalate)

Direct radiation graft polymerization of acrylic acid onto oriented poly(ethylene terephthalate) films and fibers subjected to thermal treatment and treated with structure-active solvents, such as dichloroethane and dioxane, was studied. Based on the results of thermomechanical analysis, X-ray diffraction, sorption, and acrylic acid grafting, conclusions were drawn concerning the character of structural changes in poly(ethylene terephthalate) exposed to structure-active solvents. The physicochemical properties of the graft copolymers obtained were examined, including the resistance against γ-radiation.