Biomedical subjects

A J Davison

Publications and source records attributed to A J Davison.

At least 19 recordsLinked to original sources

PubMed2001

French scallops: a new host for ostreid herpesvirus-1.

Sporadic high mortalities were reported among larval French scallops (Pecten maximus). Electron microscopy of moribund larvae revealed particles with the characteristics of a herpesvirus in association with cellular lesions. PCR and DNA sequencing showed that the virus is a variant of ostreid herpesvirus-1 that has already been described in clams and oysters. This is the first description of a herpesvirus infection of a scallop species. The virus was transmitted successfully from an extract of infected scallop larvae to uninfected scallop or oyster (Crassostrea gigas) larvae, demonstrating that it is able to infect both species. Detection of viral DNA in asymptomatic adult scallops by in situ hybridisation indicates that the herpesvirus may have been transmitted from adults to larvae. It is notable that, unlike most herpesviruses, this virus has a wide host range reflected by its ability to infect several species of marine bivalve.

Amino Acid Sequence↗

PubMed2001

Reaction of oxygen with 6-hydroxydopamine catalyzed by Cu, Fe, Mn, and V complexes: identification of a thermodynamic window for effective metal catalysis.

In the autoxidation of 6-hydroxydopamine, we investigated the reactivity of metals and metal complexes with a range of abilities to catalyse the reaction with oxygen. Comparing the catalytic effectiveness of aquo metals at pH 7.4, copper accelerated autoxidation 61-fold, iron 24-fold, manganese 7.3-fold, and vanadium 5.7-fold. Copper was thus the most effective catalyst despite being the weakest oxidant, indicating reduction of oxygen as rate limiting. EDTA, which decreases the reduction potential of Fe(III)/Fe(II), increased catalysis by iron 74% to almost that of aquo copper. Conversely, EDTA inhibited catalysis by copper, manganese, and vanadium. Desferrioxamine strongly inhibited catalysis by all of the metals. Histidine prevented catalysis by copper, accelerated catalysis by iron (43%), and had little effect on catalysis by manganese or vanadium. ADP and phytate inhibited catalysis by iron and manganese (50% or more), accelerated catalysis by vanadium (10-27%), and had no effect on catalysis by copper. The effects of the ligands largely reflected their influence on the reduction potential of the metal. Accordingly, addition of NaBr, which increases the reduction potential of Cu(II)/Cu(I), inhibited by 50%. In contrast, Na2SO4 augmented catalysis by copper 3-fold. Consistent with effects of OH- on reduction potentials and on metal coordination to 6-hydroxydopamine, an increase in pH to 8.0 decreased catalysis by copper and iron, but increased that of manganese 10-fold. In conclusion, the catalytic effectiveness of the metal-ligand complexes are largely attributable to their reduction potential, with steric accessibility playing secondary roles. The results delineate a window of catalytically effective potentials suitable for facile reduction and reoxidation by oxygen. By extension the results identify factors determining the pro- and antioxidant roles of ligands in metal mediated reduction of oxygen.

Adenosine Diphosphate↗

PubMed2001

DNA breakage induced by 1,2,4-benzenetriol: relative contributions of oxygen-derived active species and transition metal ions.

We report here the relative roles of metals and selected reactive oxygen species in DNA damage by the genotoxic benzene metabolite 1,2,4-benzenetriol, and the interactions of antioxidants in affording protection. 1,2,4-Benzenetriol induces scission in supercoiled phage DNA in neutral aqueous solution with an effective dose (ED(50)) of 6.7 microM for 50% cleavage of 2.05 microg/ml supercoiled PM2 DNA. In decreasing order of effectiveness: catalase (20 U/ml), formate (25 mM), superoxide dismutase (20 U/ml), and mannitol (50 mM) protected, from 85 to 28%. Evidently, H(2)O(2) is the dominant active species, with O(2)(*)(-) and *OH playing subordinate roles. Desferrioxamine or EDTA inhibited DNA breakage by 81-85%, despite accelerating 1,2,4-benzenetriol autoxidation. Consistent with this suggestion of a crucial role for metals, addition of cupric, cuprous, ferric, or ferrous ions enhanced DNA breakage, with copper being more active than iron. Combinations of scavengers protected more effectively than any single scavenger alone, with implications for antioxidants acting in concert in living cells. Synergistic combinations were superoxide dismutase with *OH scavengers, superoxide dismutase with desferrioxamine, and catalase with desferrioxamine. Antagonistic (preemptive) combinations were catalase with superoxide dismutase, desferrioxamine with *OH scavengers, and catalase with *OH scavengers. The most striking aspect of synergism was the extent to which metal chelation (desferrioxamine) acted synergistically with either catalase or superoxide dismutase to provide virtually complete protection. Concluding, 1,2,4-benzenetriol-induced DNA damage occurs mainly by site-specific, Fenton-type mechanisms, involving synergism between several reactive intermediates. Multiple antioxidant actions are needed for effective protection.

Catalase↗

PubMed2001

Natural history of murine gamma-herpesvirus infection.

Murine gamma-herpesvirus 68 (MHV-68) is a natural pathogen of small rodents and insectivores (mice, voles and shrews). The primary infection is characterized by virus replication in lung epithelial cells and the establishment of a latent infection in B lymphocytes. The virus is also observed to persist in lung epithelial cells, dendritic cells and macrophages. Splenomegaly is observed two weeks after infection, in which there is a CD4+ T-cell-mediated expansion of B and T cells in the spleen. At three weeks post-infection an infectious mononucleosis-like syndrome is observed involving a major expansion of Vbeta4+CD8+ T cells. Later in the course of persistent infection, ca. 10% of mice develop lymphoproliferative disease characterized as lymphomas of B-cell origin. The genome from MHV-68 strain g2.4 has been sequenced and contains ca. 73 genes, the majority of which are collinear and homologous to other gamma-herpesviruses. The genome includes cellular homologues for a complement-regulatory protein, Bcl-2, cyclin D and interleukin-8 receptor and a set of novel genes M1 to M4. The function of these genes in the context of latent infections, evasion of immune responses and virus-mediated pathologies is discussed. Both innate and adaptive immune responses play an active role in limiting virus infection. The absence of type I interferon (IFN) results in a lethal MHV-68 infection, emphasizing the central role of these cytokines at the initial stages of infection. In contrast, type II IFN is not essential for the recovery from infection in the lung, but a failure of type II IFN receptor signalling results in the atrophy of lymphoid tissue associated with virus persistence. Splenic atrophy appears to be the result of immunopathology, since in the absence of CD8+ T cells no pathology occurs. CD8+ T cells play a major role in recovery from the primary infection, and also in regulating latently infected cells expressing the M2 gene product. CD4+ T cells have a key role in surveillance against virus recurrences in the lung, in part mediated through 'help' in the genesis of neutralizing antibodies. In the absence of CD4+ T cells, virus-specific CD8+ T cells are able to control the primary infection in the respiratory tract, yet surprisingly the memory CD8+ T cells generated are unable to inhibit virus recurrences in the lung. This could be explained in part by the observations that this virus can downregulate major histocompatibility complex class I expression and also restrict inflammatory cell responses by producing a chemokine-binding protein (M3 gene product). MHV-68 provides an excellent model to explore methods for controlling gamma-herpesvirus infection through vaccination and chemotherapy. Vaccination with gp150 (a homologue of gp350 of Epstein-Barr virus) results in a reduction in splenomegaly and virus latency but does not block replication in the lung, nor the establishment of a latent infection. Even when lung virus infection is greatly reduced following the action of CD8+ T cells, induced via a prime-boost vaccination strategy, a latent infection is established. Potent antiviral compounds such as the nucleoside analogue 2'deoxy-5-ethyl-beta-4'-thiouridine, which disrupts virus replication in vivo, cannot inhibit the establishment of a latent infection. Clearly, devising strategies to interrupt the establishment of latent virus infections may well prove impossible with existing methods.

Animals↗

PubMed2001

Analysis of a novel strain of murine gammaherpesvirus reveals a genomic locus important for acute pathogenesis.

Infection of mice by murine gammaherpesvirus 68 (MHV-68) is an excellent small-animal model of gammaherpesvirus pathogenesis in a natural host. We have carried out comparative studies of another herpesvirus, murine herpesvirus 76 (MHV-76), which was isolated at the same time as MHV-68 but from a different murid host, the yellow-necked mouse (Apodemus flavicollis). Molecular analyses revealed that the MHV-76 genome is essentially identical to that of MHV-68, except for deletion of 9,538 bp at the left end of the unique region. MHV-76 is therefore a deletion mutant that lacks four genes unique to MHV-68 (M1, M2, M3, and M4) as well as the eight viral tRNA-like genes. Replication of MHV-76 in cell culture was identical to that of MHV-68. However, following infection of mice, MHV-76 was cleared more rapidly from the lungs. In line with this, there was an increased inflammatory response in lungs with MHV-76. Splenomegaly was also significantly reduced following MHV-76 infection, and much less latent MHV-76 was detected in the spleen. Nevertheless, MHV-76 maintained long-term latency in the lungs and spleen. We utilized a cosmid containing the left end of the MHV-68 genome to reinsert the deleted sequence into MHV-76 by recombination in infected cells, and we isolated a rescuant virus designated MHV-76(cA8+)4 which was ostensibly genetically identical to MHV-68. The growth properties of the rescuant in infected mice were identical to those of MHV-68. These results demonstrate that genetic elements at the left end of the unique region of the MHV-68 genome play vital roles in host evasion and are critical to the development of splenic pathology.

Animals↗

PubMed2000

DNA-breaking versus DNA-protecting activity of four phenolic compounds in vitro.

Given the paradoxical effects of phenolics in oxidative stress, we evaluated the relative pro-oxidant and antioxidant properties of four natural phenolic compounds in DNA nicking. The phenolic compounds differed dramatically in their ability to nick purified supercoiled DNA, with the relative DNA nicking activity in the order: 1,2,4-benzenetriol (100% nicking) > gallic acid > caffeic acid > gossypol (20% nicking). Desferrioxamine (0.02 mM) decreased DNA strand breakage by each phenolic, most markedly with gallate (85% protection) and least with caffeic acid (26% protection). Addition of metals accelerated DNA nicking, with copper more effective (approximately 5-fold increase in damage) than iron with all four phenolics. Scavengers revealed the participation of specific oxygen-derived active species in DNA breakage. Hydrogen peroxide participated in all cases (23-90%). Hydroxyl radicals were involved (32-85%), except with 1,2,4-benzenetriol. Superoxide participated (81-86%) with gallic acid and gossypol, but not with caffeic acid or 1,2,4-benzenetriol. With 1,2,4-benzenetriol, scavengers failed to protect significantly except in combination. Thus, in the presence of desferrioxamine, catalase or superoxide dismutase inhibited almost completely. When DNA breakage was induced by Fenton's reagent (ascorbate plus iron) the two catechols (caffeic acid and gossypol) were protective, whereas the two triols (1,2,4-benzenetriol and gallic acid) exacerbated damage.

Antioxidants↗

PubMed2000

Herpes simplex virus type 1 gene UL14: phenotype of a null mutant and identification of the encoded protein.

Herpes simplex virus type 1 (HSV-1) gene UL14 is located between divergently transcribed genes UL13 and UL15 and overlaps the promoters for both of these genes. UL14 also exhibits a substantial overlap of its coding region with that of UL13. It is one of the few HSV-1 genes for which a phenotype and protein product have not been described. Using mass spectrometric and immunological approaches, we demonstrated that the UL14 protein is a minor component of the virion tegument of 32 kDa which is expressed late in infection. In infected cells, the UL14 protein was detected in the nucleus at discrete sites within electron-dense nuclear bodies and in the cytoplasm initially in a diffuse distribution and then at discrete sites. Some of the UL14 protein was phosphorylated. A mutant with a 4-bp deletion in the central region of UL14 failed to produce the UL14 protein and generated small plaques. The mutant exhibited an extended growth cycle at low multiplicity of infection and appeared to be compromised in efficient transit of virus particles from the infected cell. In mice injected intracranially, the 50% lethal dose of the mutant was reduced more than 30,000-fold. Recovery of the mutant from the latently infected sacral ganglia of mice injected peripherally was significantly less than that of wild-type virus, suggesting a marked defect in the establishment of, or reactivation from, latent infection.

Amino Acid Sequence↗

PubMed1999

Variability and evolution of Kaposi's sarcoma-associated herpesvirus in Europe and Africa. International Collaborative Group.

OBJECTIVE: To study the evolution of Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus type 8 in Europe and Africa. DESIGN AND METHODS: PCR and sequence analysis of the variable viral membrane glycoprotein gene K1 in 58 tumour and peripheral blood samples from patients with AIDS-related Kaposi's sarcoma (KS), 'classic' (HIV-negative) KS, transplant KS, Multicentric Castleman's Disease, other lymphoproliferative disorders, and healthy KSHV-infected individuals from the UK, Denmark, Sweden, Italy, Spain, Iceland, The Faroe Islands, Greece, The Gambia and Uganda. RESULTS: Three major groups of K1 sequences were found: A, B and C, as defined previously. The K1 gene has evolved, both within and between these three groups, under positive selection. KSHV group B strains predominate in Africa and are more distant from groups A and C, found in Europe, than A and C are from each other. Within group C two subgroups, C' and C", can be identified. Subgroup C" is more closely related to group A in a region of the K1 protein and appears to be phylogenetically close to the branchpoint between A and C. Group A and C strains are currently found in both HIV-1-infected and -uninfected Europeans, and were already present in Europe before the start of the AIDS epidemic. We found some examples of closely related K1 sequences in Italy and Denmark, but in general KSHV strains in Europe did not cluster geographically. CONCLUSION: KSHV strains in East and West Africa are closely related but phylogenetically distant from those in Europe. The two major KSHV groups in Europe are more closely related, with some strains adopting an intermediate phylogenetic position. In Europe, KSHV strains may have been disseminated at least several decades ago. Variability in the K1 region is driven by selection and does not correlate with different KSHV-related pathologies or geographic regions where clinically more aggressive HIV-negative KS ('endemic' KS) is more common.

AIDS-Related Opportunistic Infections↗

PubMed1999

The descent of human herpesvirus 8.

Analysis of conserved herpesvirus genes shows that human herpesvirus 8 (HHV8) belongs to a clade of primate herpesviruses within the gamma2 sublineage. Overall, this clade has developed by cospeciation with host species. Seventeen genes of HHV8 and its nearest relatives lack simple homologues in other herpesviruses, and eight of these have known mammalian homologues, presumed to be the sources of the HHV8 versions. Comparative analyses yield further insights into the source or time of acquisition for several of these genes. All were acquired by the HHV8 lineage in the very distant past. Two unusual processes are manifest in the contemporary evolution of HHV8. First, the K1 gene is uniquely undergoing a process of extensive and positively selected substitution, of unknown significance. Secondly, the K15 gene has been substituted in some lineages by a distant homologue, presumably by recombination with an unknown herpesvirus. While available data are otherwise compatible with a cospeciational relationship between HHV8 and the human species, they do not exclude relatively recent transfer to humans from another primate host.

Chemokines, CC↗

PubMed1999

Genomic studies of the Lucké tumor herpesvirus (RaHV-1).

Ranid herpesvirus 1 (RaHV-1) is the etiological agent of the Lucké renal adenocarcinoma of the North American leopard frog Rana pipiens. Construction of cosmid libraries containing RaHV-1 DNA inserts allowed the derivation of a BamHI map for the viral genome. Summation of fragment sizes indicates that the genome is 217 kbp in size, a value in accordance with the most recent published estimate (220 kbp) obtained by field-inversion gel electrophoresis. The DNA sequence of the 39,757-bp insert in 1 cosmid (cos54) was determined and was predicted to contain 21 complete and 3 partial genes. In all, 12 genes have distant counterparts in a fish herpesvirus (ictalurid herpesvirus 1) and are present in 2 blocks, 1 of which is relatively inverted. This indicates that RaHV-1 belongs to the fish virus lineage of the herpesvirus family rather than to the lineage populated by mammalian and avian viruses. The remaining 12 genes in cos54 lack counterparts in any other herpesvirus. One of these encodes a putative DNA (cytosine-5) methyltransferase. This raises the possibility that biological processes induced in the host by RaHV-1 might involve methylation of cellular DNA by the viral enzyme.

Adenocarcinoma↗

PubMed1998

The DNA sequence of the RK strain of human herpesvirus 7.

The complete DNA sequence of human herpesvirus-7 (HHV-7) strain RK was determined following direct cloning of virion DNA fragments into a sequencing vector. The sequence was compared with the previously published complete sequences of HHV-7 strain JI and human herpesvirus-6 (HHV-6) strain U1102. Despite a very close relationship between the two HHV-7 strains, differences are apparent in regions containing tandem reiterations, particularly in the "telomeric" reiterations located near the termini of the large direct repeat at the genome ends, and in a total of 179 additional positions distributed throughout the genome (i.e., about one nucleotide difference per kbp). This extent of divergence implies that the two strains arose from an ancestral virus several thousands of years ago. Differences that affect coding potential do not cluster in particular protein-coding regions, indicating that specific HHV-7 genes have not been measurably subject to unusual evolutionary pressures since divergence. Reassessments of genetic content indicated that the HHV-7 genome contains 84 different genes, whereas the HHV-6 genome contains 85. All HHV-7 genes but 1 have direct HHV-6 counterparts, and all but 2 HHV-6 genes have HHV-7 homologues. Sequence comparisons between HHV-7 and HHV-6 provided evidence that the protein-coding regions of 11 genes are expressed by splicing.

Amino Acid Sequence↗

PubMed1998

Identification of the UL4 protein of herpes simplex virus type 1.

Herpes simplex virus type 1 gene UL4 is predicted to encode a 199-amino-acid protein with a molecular mass of 21 5 kDa. We report here identification of this protein and its localization in the nuclei of infected cells. Antisera raised against oligopeptides corresponding to the C terminus of the predicted UL4 protein were used for identification of a 25 kDa protein as the product of the UL4 gene. This protein was not detected in cells infected with a UL4 defective mutant virus, but was synthesized by coupled in vitro transcription-translation of the UL4 gene. Synthesis of the 25 kDa protein was blocked by phosphonoacetic acid, an inhibitor of DNA synthesis, indicating that the UL4 gene is expressed with gamma kinetics. Subcellular fractionation showed the protein to be localized in the nucleus. It was not detected in virions or light particles.

Amino Acid Sequence↗

PubMed1998

Characterization of the protein encoded by gene UL49A of herpes simplex virus type 1.

Herpes simplex virus type 1 (HSV-1) gene UL49A potentially encodes a primary translation product of 91 residues with a signal sequence at the N terminus and a membrane anchor domain near the C terminus. Mutants were generated in this gene and utilized to characterize the encoded protein on SDS-PAGE as a 6.7 kDa species which fractionated with infected cell membranes, was a relatively abundant virion component, and was not detectably O-glycosylated. The protein was identified by microsequencing as a 68 residue polypeptide formed by removal of 23 residues from the N terminus of the primary translation product. Cleavage of the signal sequence was also demonstrated by in vitro transcription and translation in the presence of microsomal membranes. The UL49A protein was efficiently solubilized along with envelope proteins by treatment of virions with a non-ionic detergent but only in the presence of a reducing agent, suggesting that it may be an envelope protein that is disulphide-linked to the tegument. It is apparent from mutational analysis that the 10 amino acid residues at the C terminus are not essential for synthesis of the protein, signal sequence cleavage, targeting to membranes and virions, linkage to the tegument and growth of virus in cell culture.

Amino Acid Sequence↗

PubMed1998

The DNA sequence of equine herpesvirus-4.

The complete DNA sequence of equine herpesvirus-4 (EHV-4) strain NS80567 was determined. The genome is 145597 bp in size and consists of a long unique region (UL, 112398 bp) flanked by a short inverted repeat (TRL/IRL, 27 bp) linked to a short unique region (Us, 12789 bp) flanked by a substantial inverted repeat (TRs/IRs, 10178 bp). EHV-4 is predicted to contain 76 different genes; three of these are present twice in TRs/IRs, giving a total of 79 genes. The closely related virus equine herpesvirus-1 (EHV-1) also possesses 76 different genes corresponding to those of EHV-4, but has a total of 80 genes because four are present twice in TRs/IRs. Interpretations of the coding capacity of the EHV-4 and EHV-1 genomes were refined by comparing the complete DNA sequences.

Amino Acid Sequence↗

PubMed1998

The genome of salmonid herpesvirus 1.

Salmonid herpesvirus 1 (SalHV-1) is a pathogen of the rainbow trout (Oncorhynchus mykiss). Restriction endonuclease mapping, cosmid cloning, DNA hybridization, and targeted DNA sequencing experiments showed that the genome is 174.4 kbp in size, consisting of a long unique region (U(L); 133.4 kbp) linked to a short unique region (U(S); 25.6 kbp) which is flanked by an inverted repeat (R(S); 7.7 kbp). U(S) is present in virion DNA in either orientation, but U(L) is present in a single orientation. This structure is characteristic of the Varicellovirus genus of the subfamily Alphaherpesvirinae but has evidently evolved independently, since an analysis of randomly sampled DNA sequence data showed that SalHV-1 shares at least 18 genes with channel catfish virus (CCV), a fish herpesvirus whose complete sequence is known and which is unrelated to mammalian herpesviruses. The use of oligonucleotide probes demonstrated that in comparison with CCV, the conserved SalHV-1 genes are located in U(L) in at least five rearranged blocks. Large-scale gene rearrangements of this type are also characteristic of the three mammalian herpesvirus subfamilies. The junction between two SalHV-1 gene blocks was confirmed by sequencing a 4,245-bp region which contains the dUTPase gene, part of a putative spliced DNA polymerase gene, and one other complete gene. The implications of these findings in herpesvirus taxonomy are discussed.

Amino Acid Sequence↗

PubMed1998

The herpes simplex virus type 1 U(L)17 gene encodes virion tegument proteins that are required for cleavage and packaging of viral DNA.

Previous studies have suggested that the U(L)17 gene of herpes simplex virus type 1 (HSV-1) is essential for virus replication. In this study, viral mutants incorporating either a lacZ expression cassette in place of 1,490 bp of the 2,109-bp U(L)17 open reading frame [HSV-1(deltaU(L)17)] or a DNA oligomer containing an in-frame stop codon inserted 778 bp from the 5' end of the U(L)17 open reading frame [HSV-1(U(L)17-stop)] were plaque purified on engineered cell lines containing the U(L)17 gene. A virus derived from HSV-1(U(L)17-stop) but containing a restored U(L)17 gene was also constructed and was designated HSV-1(U(L)17-restored). The latter virus formed plaques and cleaved genomic viral DNA in a manner indistinguishable from wild-type virus. Neither HSV-1(deltaU(L)17) nor HSV-1(U(L)17-stop) formed plaques or produced infectious progeny when propagated on noncomplementing Vero cells. Furthermore, genomic end-specific restriction fragments were not detected in DNA purified from noncomplementing cells infected with HSV-1(deltaU(L)17) or HSV-1(U(L)17-stop), whereas end-specific fragments were readily detected when the viruses were propagated on complementing cells. Electron micrographs of thin sections of cells infected with HSV-1(deltaU(L)17) or HSV-1(U(L)17-stop) illustrated that empty capsids accumulated in the nuclei of Vero cells, whereas DNA-containing capsids accumulated in the nuclei of complementing cells and enveloped virions were found in the cytoplasm and extracellular space. Additionally, protein profiles of capsids purified from cells infected with HSV-1(deltaU(L)17) compared to wild-type virus show no detectable differences. These data indicate that the U(L)17 gene is essential for virus replication and is required for cleavage and packaging of viral DNA. To characterize the U(L)17 gene product, an anti-U(L)17 rabbit polyclonal antiserum was produced. The antiserum reacted strongly with a major protein of apparent Mr 77,000 and weakly with a protein of apparent Mr 72,000 in wild-type infected cell lysates and in virions. Bands of similar sizes were also detected in electrophoretically separated tegument fractions of virions and light particles and yielded tryptic peptides of masses characteristic of the predicted U(L)17 protein. We therefore conclude that the U(L)17 gene products are associated with the virion tegument and note that they are the first tegument-associated proteins shown to be required for cleavage and packaging of viral DNA.

Animals↗

PubMed1997

Steering without representation with the use of active fixation.

This paper demonstrates the use of active fixation on both fixed and moving fixation points to guide a robot vehicle by means of a steering rule which, at large distances, sets the steering angle directly proportional to the deviation of gaze direction from translation direction. Steering a motor vehicle around a winding but otherwise uncluttered road has been observed by Land and Lee to involve repeated periods of visual fixation upon the tangent point of the inside of each bend. We suggest that proportional rule devised for steering in the robotic example appears applicable to the observed human performance data, providing an alternative explanation to the quadratic rule proposed by Land and Lee.

Humans↗

PubMed1996

Arsenic and chromium enhance transformation of bovine papillomavirus DNA-transfected C3H/10T1/2 cells.

Tumor promoters such as phorbol esters, teleocidin and okadaic acid increase the numbers of multilayered, transformed foci produced by BPV DNA-transfected C3H/10T1/2 cells. We questioned whether arsenic and chromium, which are known human carcinogens also enhance transformation of BPV DNA-transfected C3H/10T1/2 cells. Cr(III) potassium sulfate at 100 microM enhanced transformation by 1.4-fold, but Cr(VI) as potassium chromate did not enhance transformation, although toxicity of potassium chromate may have prevented enhancement of transformation. Sodium arsenite (As(III) at 5 microM and sodium arsenate (As(V)) at 25 microM both enhanced neoplastic transformation by 6-fold. By comparison, in previous studies, sodium orthovanadate (V(IV)) or vanadyl sulfate (V(IV)) at 4 microM enhanced numbers of transformed foci by 25-50-fold. The comparatively strong enhancement of transformation by vanadium and phorbol esters suggests that neoplastic transformation may occur by mechanisms that are common to these compounds including alteration of tyrosine phosphorylation.

Animals↗