Jerry L. Phillips

• Ph.D.
• Executive Director & Professor at University of Colorado Colorado Springs

A major concern of the adverse effects of exposure to non-ionizing electromagnetic field (EMF) is cancer induction. Since the majority of cancers are initiated by damage to a cell's genome, studies have been carried out to investigate the effects of electromagnetic fields on DNA and chromosomal structure. Additionally, DNA damage can lead to change...

We have tested an 836.55 MHz field with North American Digital Cellular (NADC) modulation in a 2-year animal bioassay that included fetal exposure. In offspring of pregnant Fischer 344 rats, we tested both spontaneous tumorigenicity and the incidence of induced central nervous system (CNS) tumors after a single dose of the carcinogen ethylnitrosour...

Rat pheochromocytoma PC12 cells have been treated with nerve growth factor (NGF) at final concentrations of 2, 4, 8, and 16 ng/ml, and then were exposed to 60-Hz, sinusoidal magnetic fields (MF) of 12.5, 25, 50, and 100 microT (rms) for 30 min. Transcript levels for both c-fos and glyceraldehyde-3 -phosphate dehydrogenase were determined by Norther...

There is uncertainty and controversy about the extent to which low level electromagnetic fields may cause deleterious effects, but even experts who are skeptical about many supposed hazards are willing to agree that electromagnetic fields even weaker than those in the MR environment can have effects under certain conditions. In order that readers c...

Molt-4 T-lymphoblastoid cells have been exposed to pulsed signals at cellular telephone frequencies of 813.5625 MHz (iDEN® signal) and 836.55 MHz (TDMA signal). These studies were performed at low SAR (average=2.4 and 24 μW g−1 for iDEN® and 2.6 and 26 μW g−1 for TDMA) in studies designed to look for athermal RF effects. The alkaline comet, or sing...

This report presents the results of a study to determine the replicability of a robust and reproducible magnetic field-induced effect reported previously by others. To this end a close collaboration was established with the original laboratory so that key procedures, research materials, reagents, and supplies were as identical as possible between o...

Rat PC12 pheochromocytoma cells have been treated with nerve growth factor and then exposed to athermal levels of a packet-modulated radiofrequency field at 836.55 MHz. This signal was produced by a prototype time-domain multiple-access (TDMA) transmitter that conforms to the North American digital cellular telephone standard. Three slot average po...

In-vitro experiments are frequently used to examine the causal mechanisms for biological change induced by chemical and physical agents. In many studies, the hope is that in-vitro experiments will lead to knowledge of mechanisms that may occur in in-vivo systems, which in turn may or may not have implications for human health and development. Unfor...

Whether or not exposure to low-level extremely low frequency magnetic fields (MFs) poses hazards to human health and development remains an unresolved issue. Central to the problem is the lack of detailed and plausible biological mechanisms to explain how such exposures could lead to human pathology. Several investigators have reported the inductio...

Deoxyspergualin (DSG) is an analog of the polyamine spergualin with preclinical evidence of activity in murine and human tumor models. This phase I study examined a 120 h continuous infusion schedule in 56 patients with refractory solid tumors at doses ranging from 80 to 2792 mg/m2/day. Dose-limiting toxicity was reversible hypotension and appeared...

There is considerable concern about potential detrimental health effects associated with exposure to environmentally relevant magnetic fields. One specific concern relates to potential effects of magnetic field (MF) exposure on reproduction and development. Consequently, an in vitro teratogenesis (developmental toxicity) assay employing embryonic D...

CCRF-CEM T-lymphoblastoid cells have been exposed to an asymmetric electromagnetic signal pulsed at 72 Hz for up to 28 hr. Following exposure, cells were lysed and extracted, and the extract was electrophoresed on SDS-polyacrylamide gels. Proteins were electroblotted onto nitrocellulose membranes and the product of the ras proto-oncogenes, p21, was...

Exposure of whole animals, isolated tissues, and cells to electromagnetic fields of various characteristics has resulted in a substantial literature detailing a wide range of effects at the morphological, physiological, biochemical, and molecular levels. In recent years, considerable effort has been devoted to defining a mechanism by which electrom...

Research into the effects of electromagnetic field (EMF) exposure on living systems is certainly not new. The literature abounds with studies detailing EMF-induced effects on whole animals, isolated tissues, cultured cells, and even subcellular systems. Nonetheless, there are those scientists who doubt the existence of many EMF-induced effects, cit...

Magnetic fields are physical, environmental agents that have been shown to produce a variety of responses in cellular and animal studies, including general changes in gene transcription. In this study, the nuclear run-off assay has been employed to assess alterations in specific gene transcription in CEM-CM3 T-lymphoblastoid cells exposed for 15-12...

Taxol is a unique mitotic inhibitor that has entered phase II investigation. Phase I studies demonstrated hypersensitivity reactions that were related to the cremophor vehicle and to the rate of drug infusion. As a result, the time span of intravenous (IV) infusion of taxol was routinely prolonged to 6 hours or beyond, and premedication with diphen...

Cells from the T-lymphoblastoid cell line, CCRF-CEM, have been exposed in vitro to a quasirectangular, asymmetric electromagnetic field pulsed at 72 Hz at 37 degrees for periods of 30 min to 24 h. RNA synthesis, assessed by incorporation of 3H-uridine, increased (relative to control cells) 2-fold after 30 min in exposed cells and achieved its great...

Tiazofurin (2-B-D-Ribofuranosylthiazole-4-Carboxamide: NSC 286193) is a nucleoside antimetabolite that acts as a potent inhibitor of IMP dehydrogenase resulting in a guanine nucleotide deprivation. Recent in vivo biochemical observations in rats bearing hepatoma suggested a correlation between depletion of guanine nucleotides and antitumor effect....

Taxol, a novel antimitotic, antitumor agent is currently undergoing Phase 1 clinical trials for the treatment of various tumors. An isocratic HPLC method has been developed for the determination of taxol in human plasma and urine. The method was then applied to the clinical pharmacokinetics of taxol following 6-h intravenous (i.v.) infusions at dos...

Fludarabine phosphate (NSC-312887) is a watersoluble adenosine analog resistant to deamination by adenosine deaminase. The agent is rapidly dephosphorylated in plasma to arabinofuranosyl-2-fluoroadenine (2FAA), the cytotoxic moiety. Because this agent has shown enhanced cytotoxicity in the human tumor cloning assay for ovarian and colorectal cancer...

Amonafide (benzisoquinolinedione, MSC 308847) is a new synthetic imide antineoplastic agent with DNA intercalative properties that has been evaluated in a phase I clinical trial. The drug was administered as a single intravenous (IV) infusion over 30 to 120 minutes repeated every 28 days. Ninety-five courses of therapy at doses ranging from 18 to 1...

Expression of transferrin receptors (TFR) is required for lymphocyte proliferation. Treatment of lymphoblastic leukemia cell lines with phorbol diester tumor promoters decreases proliferation and induces differentiation. Among changes induced by phorbol diesters is decreased cell surface expression of TFR. To elucidate effects of phorbols on lympho...

We have utilized [3H]diacetyl-didemnin B ([3H]DB) in a series of in vitro experiments to determine the time course of equilibration of [3H]DB between plasma and blood cells, the distribution of [3H]DB among blood cells, and the distribution of [3H]DB in plasma. Within 45-60 min at 37 degrees C, approximately 55% of [3H]DB added to whole blood remai...

Didemnin B (NSC-325319), a cyclic depsipeptide isolated from a marine tunicate, has been evaluated in a Phase I trial. The drug was administered in a single intravenous infusion in 150 cm3 of normal saline every 30 min given every 28 days. Forty-three patients received 80 courses of the drug at doses ranging from 0.14 to 4.51 mg/m2. The dose-limiti...

We compared transferrin receptor (TfR) expression on human peripheral blood lymphocytes (PBL) activated by phorbol myristate acetate (PMA) or L-phytohemagglutinin (LPHA) using two techniques: (1) 125I-iron-saturated transferrin (FeTf) binding, (2) reactivity with monoclonal anti-TfR antibodies--OKT9 and B3/25. These monoclonal antibodies do not blo...

Iron transferrin has been found to induce a mean 10-fold increase in the activity of protein kinase C in CCRF-CEM cells. This increase was not detectable up to 45 min after treatment of cells with iron transferrin, although after 60 min, a maximal increase in enzyme activity was observed. Similarly, iron transferrin at concentrations of 0.1-0.5 mic...

The role of target cell transferrin receptors (TfR) in natural killer (NK) cell-induced cytolysis has been studied using Colo 205 cells in which prior exposure to 60 Hz electromagnetic fields produced constitutive expression of maximum numbers of TfR. It was found that NK cell cytolysis was decreased in those cells expressing the highest levels of...

Expression of transferrin receptors (TfR) by activated lymphocytes is necessary for lymphocyte DNA synthesis and proliferation. Regulation of TfR expression, therefore, is a mechanism by which the lymphocyte's proliferative potential may be directed and controlled. We studied mechanisms by which lymphoblastoid cells modulate TfR expression during t...

Fludarabine phosphate, an investigational water-soluble adenosine analog, was administered ip to five miniature swine at doses of 10, 16, and 25 mg/m2. Blood and peritoneal fluid samples were collected for 4 hours following drug administration and were submitted to high-performance liquid chromatographic analysis for the concentrations of the depho...

Two human colon cancer cell lines, Colo 205 and Colo 320 DM, have been studied for their responses to 60 Hz-generated electromagnetic fields (EMF) using soft agar cloning and monoclonal antibody binding assays to assess exposure-induced changes. Cellular responses have been studied after 24 h continuous exposure of cells concurrently to four experi...

125I-Labeled human transferrin was used to study the binding of transferrin to Colo 320 DM and Colo 205 human cell lines derived from adenocarcinomas of the colon. Although transferrin uptake was greater in both cases at 37 degrees than at 4 degrees it was found that slightly greater than two-thirds of the transferrin associated with the cells at 3...

Characterization of the pharmacokinetics of 2-FLAA has been completed in seven patients receiving 18 or 25 mg/m2 daily X 5 of 2-FLAMP over 30 min. Assuming 2-FLAMP was instantaneously converted to 2-FLAA, the plasma levels of 2-FLAA declined in a biexponential fashion. Computer fitting of the plasma concentration-time curves yielded an average dist...

9-beta-D-Arabinofuranosyl-2-fluoroadenine 5'-monophosphate (NSC 312887) is a new purine antimetabolite that has been evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. infusion over a period of 30 min once each day for 5 consecutive days, repeated at 4-week intervals. Thirteen patients received 30 cours...

Using a single-incubation two-site immunoradiometric assay, ferritin levels in human peripheral blood lymphocytes have been quantitated up to 72 h in culture. Ferritin levels were found to increase markedly when the cells were treated with phytohemagglutinin or with iron transferrin (in the presence or absence of phytohemagglutinin). On the other h...

Apothionein was prepared from rat liver metallothionein-II. To this, zinc, as zinc acetate, was re-added in a stepwise fashion to yield a series of complexes with ratios of metal to protein varying from 1:1 to 7:1. The Stokes' radius of the apoprotein and each zinc-metallothionein complex was then determined by gel filtration. A plot of atoms Zn/mo...

Lymphocytes were obtained from two patients with paroxysmal nocturnal hemoglobinuria as well as from apparently healthy controls and from patients with acute lymphoblastic leukemia and chronic lymphocytic leukemia. Subsequently, several aspects of zinc metabolism were studied in vitro in short-term cultures of these lymphocytes in order to assess l...

Immobilized subtilisin Novo was used for the cleavage of iron-saturated ovotransferrin (Fe2OT) into separate NH2- and CO2H-terminal iron-binding fragments, designated as FeNF and FeCF, respectively. The Mr of each fragment is 39,000. The purified fragments show major differences in the content of histidine, alanine, and methionine. Both apo-NH2- an...

Human peripheral blood lymphocytes were incubated with [(65)Zn] zinc transferrin and with and without phytohemagglutinin for 1, 2, 4, 10, 24, 48, 72, and 96h. Gel filtration of cytoplasmic fractions obtained from these lymphocytes was then performed to determine the molecular distribution of incorporated zinc as a function of time in culture. The d...

The distribution of transferrin-bound zinc incorporated by phytohemagglutinin-stimulated and unstimulated human lymphocytes has been studied as a function of time in four subcellular fractions (nuclei, mitochondria, microsomes, and soluble). In untreated lymphocytes, the percent of total incorporated zinc in each fraction remains relatively constan...

Incubation of human peripheral blood lymphocytes with zinc transferrin (with or without phytohemagglutinin) induces the synthesis of protein that elutes from a Sephadex G-75 column at aV e/V o value corresponding to a molecular weight of 6600. Synthesis depends on the concentration of zinc transferrin in the medium and is sensitive to actinomycin D...

Uptake of transferrin-bound zinc was stimulated in phytohemagglutinin-treated human lymphocytes as compared to untreated lymphocytes. Stimulation of zinc uptake depended upon the concentration of phytohemagglutinin and was maximal for the first hour after addition of phytohemagglutinin to lymphocyte cultures. Thereafter, increased zinc uptake decli...

Phytohemagglutinin and poly-L-ornithine were tested for their ability to stimulate uptake of transferrin-bound zinc by lymphocytes from both normal donors and donors with chronic lymphocytic leukemia. The ratio of zinc uptake in poly-L-ornithine cultures to zinc uptake in phytohemagglutinin cultures was 0.9 +/- 0.3 for leukemic lymphocytes and 1.9...

Radioiodinated zinc transferrin has been found to interact with human lymphocytes in a manner characterized by rapid binding, saturability, reversibility, and specificity. Each lymphocyte can bind a maximum of approximately 61,000 molecules of zinc transferrin with an association constant of 4 x 10/sup 7/ M/sup -1/. Binding is strongly inhibited by...

Metals have long been recognized as essential constituents of living systems, and one trace metal that has been studied extensively is zinc. In addition to serving a structural or catalytic role in numerous enzymes, zinc has been linked to certain key cellular and physiologic processes. For instance, zinc, accelerates wound healing, is involved in...

Radioiodinated human serum transferrin has been found to interact with polypropylene culture tubes in a manner that mimics the specific binding of a protein to a cellular receptor. The magnitude of this transferrin-culture tube interaction is such that any true binding of the protein to cells present is masked. Characteristics of this non-specific...

A simple and highly reproducible method was developed for the dissociation of ovine luteal tissue into isolated cell suspensions using a crude collagenase preparation in Medium 199. The procedure required less than 3 hr. The mean yield of cells was 81.8 ± 9.1 × 106 cells/g tissue. The resulting cell preparation synthesized progesterone and responde...

The uptake and retention of 3H-estradiol by the ovine corpus luteum (induced by superovulation) was maximal through days 8-12 of the cycle with little or no uptake and retention during luteinization or regression. LH, but not FSH or prolactin, inhibited the uptake and retention of estradiol via stimulation of progesterone synthesis.

In serum-free cultures of phytohemagglutinin-stimulated human lymphocytes, iron transferrin causes enhanced uptake of both tritiated thymidine and tritiated uridine over that seen with only phytohemagglutinin. This effect is specific for the iron transferrin complex, no enhancement produced by either free iron(III) or apotransferrin. Iron bound to...

Cleavage of ovotransferrin with cyanogen bromide at 4° resulted in the production of four fragments which were purified by Bio-Gel P-150 chromatography using 1 M propionic acid as the eluent. Iron-binding activity was found only in the largest fragment, denoted CF1 (mol wt 36,000), which consisted of two polypeptides linked by disulfide bonds. CF1...

Zinc transferrin, when added to serum-free cultures of phytohemagglutinin-stimulated human lymphocytes, causes an increase in deoxyribonucleic acid synthesis over that seen with phytohemagglutinin alone, as judged by the uptake of tritiated thymidine. This effect is not seen with zinc acetate, zinc albumin, or zinc ovotransferrin. Zinc transferrin...

Cyanogen bromide cleavage of ovotransferrin, an iron-binding protein from chicken egg white, followed by reduction and carboxymethylation of each initially liberated fragment, produced a total of eight distinct polypeptides, ranging in molecular weight from 2700 to 35,000 daltons. The total molecular weight of the polypeptides accounts for the mole...

Nitration of iron-free ovotransferrin with tetranitromethane resulted in the disappearance of all 20 tyrosine residues with a complete loss of iron-binding activity. Under the same conditions, however, iron-saturated ovotransferrin showed the disappearance of 13-14 tyrosines with complete retention of iron-binding activity. The modified tyrosines w...

Short-time iodination of metal-free ovotransferrin indicated that the tyrosine groups involved in the iron-binding activity are indistinguishable from other structural tyrosines. Modification of a minimum of 14 tyrosine residues per molecule of protein was required to achieve a complete loss of metal-binding activity. In contrast, a maximum modific...

The reaction of cyanogen bromide with ovotransferrin produced three polypeptide fragments, which were recovered in a mole ratio of 1:1:1. For every mole of ovotransferrin cleaved and fractionated, 2 moles of each fragment was recovered. Molecular weights of the fragments were estimated as 21,000, 9400, and 7000, the sum of which is approximately on...

Short-time exposure of ovotransferrin to periodate oxidation at pH 8.5 and 5 resulted in the destruction of three and five tyrosine residues, respectively, per mole of the protein and an almost complete loss in its chromogenic activity. In contrast, the Fe-ovotransferrin complex retained its full chromogenic activity in the presence of periodate an...