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Biomedical subjects

C N Rafferty

Publications and source records attributed to C N Rafferty.

At least 19 recordsLinked to original sources
PubMed2001

Large granular lymphocytic (LGL) leukemia in rats exposed to intermittent 60 Hz magnetic fields.

An animal model for large granular lymphocytic (LGL) leukemia in male Fischer 344 rats was utilized to determine whether magnetic field exposure can be shown to influence the progression of leukemia. We previously reported that exposure to continuous 60 Hz, 1 mT magnetic fields did not significantly alter the clinical progression of LGL leukemia in young male rats following injection of spleen cells from donor leukemic rats. Results presented here extend those studies with the following objectives: (a) to replicate the previous study of continuous 60 Hz magnetic field exposures, but using fewer LGL cells in the inoculum, and (b) to determine if intermittent 60 Hz magnetic fields can alter the clinical progression of leukemia. Rats were randomly assigned to four treatment groups (18/group) as follows: (1) 1 mT (10 G) continuous field, (2) 1 mT intermittent field (off/on at 3 min intervals), (3) ambient controls ( < 0.1 microT), and (4) positive control (5 Gy whole body irradiation from cobalt-60 four days prior to initiation of exposure). All rats were injected intraperitoneally with 2.2 x 10(6) fresh, viable LGL leukemic spleen cells at the beginning of the study. The fields were activated for 20 h per day, 7 days per week, and all exposure conditions were superimposed over the natural ambient magnetic field. The rats were weighed and palpated for splenomegaly weekly. Splenomegaly developed 9-11 weeks after transplantation of the leukemia cells. Hematological evaluations were performed at 6, 8, 10, 12, 14, and 16 weeks of exposure. Peripheral blood hemoglobin concentration, red blood cells, and packed cell volume declined, and total white blood cells and LGL cells increased dramatically in all treatment groups after onset of leukemia. Although the positive control group showed different body weight curves and developed signs of leukemia earlier than other groups, differences were not detected between exposure groups and ambient controls. Furthermore, there were no overall effects of magnetic fields on splenomegaly or survival in exposed animals. In addition, no significant and/or consistent differences were detected in hematological parameters between the magnetic field exposed and the ambient control groups.

Animals↗
PubMed2000

Assessing the potential carcinogenic activity of magnetic fields using animal models.

We update our 1997 publication by reviewing 29 new reports of tests of magnetic fields (MFs) in six different in vivo animal models of carcinogenesis: 2-year, lifetime, or multigeneration exposure studies in rats or mice; and promotion/progression models (rat mammary carcinoma, rat liver focus, mouse skin, several models of human leukemia/lymphoma in rats and mice, and brain cancer in rats). Individual experiments are evaluated using a set of data quality criteria, and summary judgments are made across multiple experiments by applying a criterion of rough reproducibility. The potential for carcinogenicity of MFs is discussed in light of the significant body of carcinogenesis data from animal bioassays that now exists. Excluding abstracts, approximately 80% of the 41 completed studies identified in this and our previous review roughly satisfy data quality criteria. Among these studies, the criterion for independent reproducibility is not satisfied for any positive results but is satisfied for negative results in chronic bioassays in rats and mice and for negative results in both promotion and co-promotion assays using the SENCAR mouse skin model. Results of independent replication studies using the rat mammary carcinoma model were conflicting. We conclude that long-term exposure to continuous 50- or 60-Hz MFs in the range of 0.002-5 mT is unlikely to result in carcinogenesis in rats or mice. Though results of most promotion/progression assays are negative, a weak promoting effect of MFs under certain exposure conditions cannot be ruled out based on available data.

Animals↗
PubMed2000

Leukemia and lymphoma incidence in rodents exposed to low-frequency magnetic fields.

A weak association between residential or occupational exposure to electric and magnetic fields (50/60 Hz fields) and an increased incidence of leukemia has been reported. Numerous animal studies have evaluated the potential association between magnetic-field exposure and leukemia. These include long-term (up to 2(1/2) years) bioassays, initiation/promotion studies, investigations in transgenic models, and tumor growth studies. Exposure to 60 Hz circularly polarized magnetic fields at 1,400 microT for 28 months did not affect lymphoma incidence in mice. The study included over 2000 C57BL/6J mice. In another study, 1000 B6C3F(1) mice exposed to 60 Hz magnetic fields up to 1000 microT for 2 years showed no increase in lymphomas. Approximately 400 transgenic Emu-Pim1 mice exposed to 50 Hz fields up to 1000 microT for up to 18 months had no increased incidence of leukemia. Similarly, Trp53(+/-) mice and Pim1transgenic mice exposed to 60 Hz magnetic fields for 23 weeks showed no increased incidence of lymphoma. Three studies in F344 rats exposed to 50 or 60 Hz magnetic fields up to 5 mT showed no increased incidence of leukemia. The combined animal bioassay results are nearly uniformly negative for magnetic-field exposures enhancing leukemia and weaken the possible epidemiological association between magnetic-field exposures and leukemia in humans as suggested by epidemiological data.

Animals↗
PubMed1999

Clinical progression of transplanted large granular lymphocytic leukemia in Fischer 344 rats exposed to 60 Hz magnetic fields.

The purpose of this study was to determine if 60 Hz magnetic fields can alter the clinical progression of leukemia in an animal model. Large granular lymphocytic (LGL) leukemia cells from spleens of leukemic rats were transplanted into young male Fischer 344 rats, producing signs of leukemia in approximately 2-3 months. The animals were randomly assigned to 4 treatment groups (108/group) as follows: 1) 10 G (1.0 mT) linearly polarized 60 Hz magnetic fields, 2) sham exposed [null energized unit with residual 20 mG (2 microT) fields], 3) ambient controls [<1 mG (0.1 [microT)], and 4) positive controls (a single 5 Gy whole body exposure to 60Co 4 days prior to initiation of exposure). All rats were injected intraperitoneally (ip) with 2.2 x 10(7) LGL leukemic cells at the initiation of exposure or sham exposure. The magnetic fields were activated for 20 h/day, 7 days/week, allowing time for animal care. The experimental fields were in addition to natural ambient magnetic fields. Eighteen rats from each treatment group were bled, killed, and evaluated at 5, 6, 7, 8, 9, and 11 weeks of exposure. Peripheral blood hematological endpoints, changes in spleen growth, and LGL cell infiltration into the spleen and liver were measured to evaluate the leukemia progression. No significant or consistent differences were detected between the magnetic field exposed groups and the ambient control group, although the clinical progress of leukemia was enhanced in the positive control animals. These data indicate that exposure to sinusoidal, linearly polarized 60 Hz, 10 G magnetic fields did not significantly alter the clinical progression of LGL leukemia. Furthermore, the data are in general agreement with previous results of a companion repeated-bleeding study in which animals were exposed for 18 weeks.

Animals↗
PubMed1997

Testing electromagnetic fields for potential carcinogenic activity: a critical review of animal models.

In order to assess the potential of electromagnetic fields (EMF) to influence the process of carcinogenesis, it will be necessary to supplement epidemiological studies with controlled laboratory studies in animals. There are now a number of suitable assays available that focus on different histopathological forms of cancer and on different stages of carcinogenesis--induction, promotion, progression. In this review we discuss eight major systems in the context of this generalized carcinogenesis paradigm. Our aim is to bring together what is currently known about the biology of carcinogenesis in these systems in order to provide a context for evaluating EMF results as they become available. We also critically discuss EMF test results that have so far been obtained in the animal models reviewed. Most of the 19 completed studies identified were negative. However, suggestive positive results were reported in three promotion assays (in rat mammary gland, in rat liver, and in mouse skin), and in one multigeneration study in mice. Results in the rat liver assay and in the multigeneration study have only been reported in abstract form and cannot be adequately evaluated. Positive results reported in both the rat mammary gland and the mouse skin systems are of weak statistical significance and have not been independently replicated. However, it may be of interest that effects in both systems appear primarily to involve the progression stage of carcinogenesis. We suggest that more definitive conclusions as to the carcinogenic potential of EMF may require expanded test protocols that reinforce traditional carcinogenesis end points with biochemical or other parameters reflective of biological processes known to be associated with carcinogenesis in the different systems.

Animals↗
PubMed1997

Can low-level 50/60 Hz electric and magnetic fields cause biological effects?

Some epidemiological studies have suggested that exposure to ambient, low-level 50/60 Hz electric and magnetic fields (EMFs) increases risk of disease. Whether this association has a causal basis depends in part on whether the electrical, chemical and mechanical "signals" induced within living cells by ambient EMFs are detectable in the complex milieu of voltages, currents and forces present within the living organism. Magnetic responsiveness has been found in some animals and bacteria; aquatic animals (e.g. sharks and rays) can sense weak electric fields. We outline the physics of several mechanisms by which EMFs may interact: (1) Energy transfer by acceleration of ions and charged proteins modifies cell membranes and receptor proteins; however, EMF energies are far below those typical of biomolecules in the cell. (2) Electric fields induced inside the body exert force on electric charges and electric moments; however, these forces are considerably smaller than typical biological forces. (3) The magnetic moments of ferromagnetic particles and free radical molecules interact with magnetic fields, but magnetic-moment sensory cells have not been found in humans, and modification of radical recombination rates by EMFs in a biological system is highly problematic. (4) Resonant interactions involve EMFs driving vibrational or orbital transitions in ion-biomolecule complexes; these mechanisms conflict with accepted physics, and many experimental tests have not found the predicted effects. (5) Temporal averaging or spatial summation can improve the ratio of "signal" to "noise" in any system, but this "mechanism" requires biological structures and neural processes having the necessary capabilities of EMF detection and temporal averaging that have not been found in humans. In summary, biological effects in humans due to extremely low-frequency EMFs of the order of those found in residential environments [< or = 2 microT (< or = 20 mG)] are implausible based on current understanding of physics and biology. Biological effects in humans at higher fields [> 10 microT (> 100 mG)] might reach plausibility as a result of time-averaging in combination with a magnetic-moment transduction mechanism; but even here, neither specialized EMF transduction structures nor appropriate averaging networks have been demonstrated. The bypothesis that the epidemiological associations observed between 50/60 Hz EMFs and disease reflect a causal relationship is not supported by what is known about mechanisms.

Animals↗
PubMed1996

Exposure to 60 Hz magnetic fields does not alter clinical progression of LGL leukemia in Fischer rats.

Associations between exposure to 60-Hz magnetic fields in residential and occupational environments and the incidence of leukemia and other cancers has been suggested by the results of a number of epidemiology studies. To address these potential associations, a study has been conducted to determine if 60-Hz magnetic fields can alter the clinical progression of leukemia. In the large granular lymphocytic (LGL) leukemia model, spleen cells from aged leukemic rats were transplanted into young, male Fischer 344 rats, producing leukemia in a relatively short period. A total of 72 animals were randomly assigned to four treatment groups (18/group) as follows: (1) 10 G; (2) sham exposed (null energized field) (approximately 20 mG); (3) ambient controls (<1 mG); and (4) positive controls (5 Gy whole body irradiation from Cobalt-60, 4 days before initiation of exposure). At the initiation of exposure or sham-exposure, all rats were injected (i.p.) with 2.2x10(7) fresh, viable, LGL leukemia cells. The magnetic fields were activated for 20 h per day, 7 days per week; all exposure conditions were superimposed over the natural ambient magnetic field. Eighteen rats from each treatment were bled at weeks 0, 2, 4, 5, 6, 7, 8 and 10 to monitor, in the same set of animals, the clinical progression of the LGL disease and survival of the animals. Peripheral blood hematological changes were monitored to evaluate the progression of the leukemia. In general, no significant or consistent differences were detected between the magnetic field exposed and the ambient field control groups, although some inconsistent and random differences were occasionally observed. These data indicate that the 10 G magnetic fields did not significantly alter the clinical progression of LGL leukemia in Fischer 344 rats.

Animals↗
PubMed1992

Dosimetry Workshop: extremely-low-frequency electric and magnetic fields.

A workshop on the dosimetry of extremely-low-frequency fields was held to assess current knowledge in this field and to develop a set of recommendations for new research that meets the needs of health risk assessment, in particular, the assessment of cancer risk. The workshop was sponsored by the Electric Power Research Institute and was held on March 20-22, 1991, in Carmel, California. Major topics of the workshop were microdosimetry of induced electric fields, scaling of induced fields among biological systems from cells to humans, and the problem of defining a biologically effective "dose." A number of research recommendations were developed, the most important of which are to (1) characterize the natural background electric and magnetic fields in tissues and near cells, (2) improve experimental exposure geometries to allow accurate characterization of induced fields in samples, (3) design experiments to distinguish between electric and magnetic field mechanisms, (4) develop standard in vitro biological systems with reproducible and well-established responses to fields, and (5) develop definition of dose with respect to fields at the primary site of interaction.

Electromagnetic Fields↗
PubMed1980

Tryptophan in bovine rhodopsin: its content, spectral properties and environment.

The tryptophan content of purified bovine rhodopsin was obtained by two independent methods: direct analysis of hydrolysates prepared by digestion of opsin with methanesulfonic acid containing 0.2% 3-(2-aminoethyl)indole and a computer-assisted analysis of the near-UV spectrum of rhodopsin. Both methods gave a value of eight tryptophan residues per rhodopsin. Based on the near-UV spectral analysis, the light-induced difference spectrum of rhodopsin, and the susceptibility of residues to oxidation by N-bromosuccinimide, we concluded that approximately half of the tyrosine and tryptophan residues are shielded to some extent from the aqueous solvent, that two of the tryptophan residues are in very apolar environments, and that following light excitation at least one of these tryptophan residues and several tyrosines are exposed to an aqueous environment. Analysis of rhodopsin absorption in the far-UV indicated that below 240 nm, approximately half of the absorption is due to aromatic residues and that the other half is largely due to the peptide bond. The effect of illumination on secondary structure is to induce a loss in helical structure, calculated to involve 35% of the amino acid residues in purified rhodopsin. If light-induced changes in secondary structure are specifically excluded, most of these results can be extended to bovine rod outer segment membranes.

Amino Acids↗
PubMed1979

The orientations of reaction center transition moments in the chromatophore membrane of Rhodopseudomonas sphareroides, bases on new linear dichroism and photoselection measurements.

Chromatophore membranes from Rhodopseudomonas sphaeroides were oriented by drying suspensions on the surfaces of glass slides, Polarized spectra of light-induced absorption changes were obtained between 500 and 1000 nm. As observed earlier, these spectra showed negative bands, reflecting photooxidation of the bacteriochlorophyll 'special pair' in the reaction centers, centered near 870, 810, 630 and 600 nm. These bands have been designated BY1, BY2, BX1 and BX2, respectively, corresponding to two QY transitions and two QX transitions of the dimeric special pair. We found the BY1 and BX1 transition moments to be parallel (within 20 degrees) to the plane of the membrane, whereas the BX2 moment makes an angle of 55--63 degrees with the plane. Using the photoselection technique we found that the angle between the BY1 and BX1 transition moments is 30 degrees, while that between BY1 and BX2 is 75 degrees. The BX1 and BX2 moments were found to be orthogonal, consistent with the prediction of molecular exciton theory for a dimer. By combining these data, we have calculated the orientations of the transition moments of the bacteriochlorophyll dimer in spherical polar coordinates, with the pole of the coordinate system normal to the plane of the membrane. The orientations of the QY and QX transition moments of the two bacteriopheophytin molecules in the reaction center were also computed in this coordinate system by transforming the data reported by Clayton, C.N., Rafferty, R.K. and Vermeglio, A. ((1979) Biochim. Biophys. Acta 545, 58--68). We have derived the transformation equations for two polar coordinate systems: in one, the pole is an axis of symmetry as defined by the orientations of purified reaction centers in stretched gelatin films (Rafferty, C.N. and Clayton, R.K. (1979) Biochim. Biophys. Acta 545, 106--121). In the other, the pole is normal to the plane of the chromatophore membrane. These two polar axes are approximately orthogonal.

Bacterial Chromatophores↗
PubMed1979

The orientations of transition moments in reaction centers of Rhodopseudomonas sphaeroides, computed from data of linear dichroism and photoselection measurements.

Linear dichroism measurements of reaction centers of Rhodopseudomonas sphaeroides in stretched gelatin films have yielded angles that various optical transition moments make with an axis of symmetry in the reaction center. Photoselection experiments have yielded angles that certain transition moments make with each other. We have combined these data so as to compute the orientations of the Qx and Qy transition moments of the two molecules of bacteriopheophytin and of the bacteriochlorophyll special pair (photochemical electron donor) in the reaction center. Orientations are expressed in spherical polar coordinates with the symmetry axis as the pole. We have also computed additional angles between pairs of transition moments. In this treatment we have assumed that the bacteriopheophytins are independent monomers with little or no exciton coupling.

Bacteriochlorophylls↗
PubMed1979

Linear dichroism and the orientation of reaction centers of Rhodopseudomonas sphaeroides in dried gelatin films.

Aqueous mixtures of reaction centers of Rhodopseudomonas sphaeroides and gelatin were dried to form thin films. Following hydration, these films were stretched as much as two to three times their original length. Polarized absorption spectra showing linear dichroism were obtained for both unstretched and stretched films, with the planes and stretching axes of the films mounted in various geometries relative to the electric vector of the measuring beam. These data were analyzed in terms of the following model: Reaction centers possess an axis of symmetry that is fixed in relation to the reaction center structure. In unstretched films this axis is confined to the film plane and oriented at random within the plane. In stretched films the symmetry axis is aligned with the direction of stretching. In both preparations reaction centers are distributed randomly with respect to rotation about the axis of symmetry. The data are consistent with this model when the analysis acknowledges less than perfect orientation. For perfect orientation in a stretched film the model predicts uniaxial symmetry about the axis of stretching. The approach to this condition was examined with films stretched to different extents. Extrapolation yielded dichroic ratios for the ideal case of perfect orientation, and allowed calculation of the angles between the axis of symmetry and the various optical transition dipoles in the reaction center. This treatment included the two absorption bands of the bacteriochlorophyll 'special pair' (photochemical electron donor) in the Qx region, at 600 and 630 nm, which we were able to resolve in light minus dark difference spectra.

Darkness↗
PubMed1979

Photooxidation of antenna bacteriochlorophyll in chromatophores from carotenoidless mutant Rhodopseudomonas sphaeroides and the attendant loss of dimeric exciton interaction.

Intense continuous illumination of purified chromatophores from carotenoidless mutant Rhodopseudomonas sphaeroides results in progressive photooxidative loss of the near infrared absorption band near 860 nm assigned to antenna bacteriochlorophyll. The quantum yield of this reaction is low, approximately 1.7 x 10(-5). The loss in near infrared absorption is accompanied by a proportional shift in the absorption maximum to shorter wavelengths. The double circular dichroism feature in the near infrared decreases at a faster rate than does the absorbance. These results are explained by a model in which the antenna bacteriochlorophyll, initially associated as dimers (lambda(max) = 860.2 nm), is progressively converted to the monomeric state (lambda(max) = 851.9 nm). The wavelength shift is attributed to disruption of exciton coupling in the dimer. Acetone/methanol extraction indicates that the maximum molar extinction coefficients of the dimer and monomer do not differ by more than 4%. The occurrence of an absorption maximum at 852 nm for monomeric bacteriochlorophyll in a protein complex demonstrates that it is not necessary to invoke aggregation of the chromophores as the origin of the shift from 770 nm in typical organic solvents.

Journal Article↗
PubMed1977

Spectral studies on the conformation of rhodopsin.

A summary is given of visible and ultraviolet spectral studies which deal with the conformation of rhodopsin in situ and solubilized with detergent. Emphasis is placed on studies which give specific information about the macromolecular structure and which set quantitative limits on the magnitude of light-induced conformational changes.

Animals↗
PubMed1977

Circular dichroism, optical rotatory dispersion, and absorption studies on the conformation of bovine rhodopsin iw situ and solubilized with detergent.

Circular dichroism, optical rotatory dispersion and absorption of rhodopsin, the visual pigment of bovine rod outer segment membranes, were studied in situ and in membranes solubilized with various detergents. The alpha-helical content of the membrane protein is approximately 30%. The membrane protein possesses little beta-structure. Solubilization of the membrane by the detergents, Emulphogene BC-720 and cetyltrimethylammonium salts, results in loss of protein helical structure and perturbation of aromatic residues. These effects are not observed on digitonin solubilization. In regard to the structural stability of the membrane during bleaching, the following conclusions were reached: (1) Delocalized conformational changes of rhodopsin in situ involving secondary and/or tertiary structure are very unlikely. (2) Localized conformational changes of rhodopsin in situ involving secondary structure must be limited to the involvement of no more than three amino acid residues and localized conformational changes involving tertiary structure must be limited to very short segments of the protein chain containing, at the most, only a few aromatic residues. (3) Large changes in the interaction of lipid and protein moieties of the membrane are unlikely. (4) The detergents, Emulphogene, cetyltrimethylammonium salts, and digitonin, significantly decrease the conformational stability of rhodopsin as compared to the in situ conditions. The effect is smaller with digitonin. Evidence is presented against a proposed mechanism by which optical activity of the prosthetic group, retinal, is induced by resonance coupling of the transition dipoles of retinal and the lowest energy transitions of the aromatic groups of the apoprotein, opsin. A mechanism in which atropisomers of retinal are preferentially bound by opsin is consistent with the present results. The optical activity of the prosthetic group is markedly changed upon solubilization of the membrane by detergent. This change in optical activity is probably coupled to changes in conformation of the protein moiety induced by solubilization.

Animals↗