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Biomedical subjects

F Breitburd

Publications and source records attributed to F Breitburd.

32 records · Page 2Linked to original sources
PubMed1985

A type-II DNA topoisomerase and a catenating protein from the transplantable VX2 carcinoma.

It has recently been suggested that topoisomerases could be important targets for several DNA intercalating drugs used in cancer therapy. This prompted us to purify and characterize a type II topoisomerase in a highly tumorigenic transplantable rabbit tumor isolated from a skin carcinoma associated with cottontail rabbit papillomavirus. We have found that the decatenating activity present in tumor cells was 40-100 times higher than that in the rabbit liver, while no activity could be found in skin extracts. The type II topoisomerases purified from tumor and liver cells consist of two subunits with molecular masses of about 160 kDa. The conditions of the reactions of relaxation, unknotting and decatenation catalyzed by these topoisomerases II were found to be similar to those observed with enzymes of other eukaryotic cells. In the course of the purification of the VX2 enzyme, we isolated and characterized a protein of about 30 kDa in whose presence the topoisomerase II was able to catenate very efficiently supercoiled DNA molecules. This protein has the same electrophoretic mobility as an H1-2 histone, and cross-reacts with an anti-H1 antiserum. The VX2 topoisomerase II as well as the VX2 tumor should constitute useful models for assays of antitumoral drugs.

Animals↗
PubMed1985

Two Shope papillomavirus-associated VX2 carcinoma cell lines with different levels of keratinocyte differentiation and transplantability.

Two cell lines, named VX2T and VX2R, were isolated from the transplantable VX2 carcinoma, a wholly anaplastic tumor established from a carcinoma induced by the Shope cottontail rabbit papillomavirus (CRPV) (J.G. Kidd and P. Rous, J. Exp. Med. 71:813-838, 1940). The CRPV genome was found to be maintained and transcribed in both cell lines, as in the VX2 carcinoma. The VX2T cells retained the tumor-producing capacity in the rabbit and the low expression of epidermal keratinocyte differentiation of the VX2 tumor cells. The VX2R cells, although tumorigenic for nude mice, were no longer serially transplantable in the rabbit and expressed differentiated functions of keratinocytes. These data indicate that the anaplastic characteristic and the transplantability of VX2 carcinoma cells to immune competent allogenic hosts may be lost without any detectable modification of the physical state and transcription of the CRPV genome.

Animals↗
PubMed1985

Multiple cutaneous papillomas and carcinomas that develop spontaneously in a mouse mutant, the repeated epilation heterozygote Er/+.

After a chance observation that multiple cutaneous papillomas and squamous cell carcinomas occurred in 2 adult mice heterozygous for the repeated epilation gene Er, we surveyed a panel of 10 +/+ (wild type) and 30 Er/+ (heterozygous) mice from birth to over 2 years of age. Homozygous Er/Er mice could not be included since their defect is lethal at birth. Whereas no cutaneous tumors developed in the +/+ mice, 20 of the Er/+ mice, males and females, had developed 1-5 cutaneous papillomas and at least 1 cutaneous invasive squamous cell carcinoma by 2 years of age. No lesions were seen in mice younger than 6 months old. Although almost all Er/+ mice died with their tumor burden, no metastases have yet been proven histologically. The Er/+ mouse should serve as a useful model for the exploration of genetic factors in cutaneous squamous cell carcinomas in humans.

Alopecia↗
PubMed1984

Monoclonal antibodies to the major capsid protein of human papillomavirus type 1.

Two stable monoclonal hybridoma cell lines secreting type-specific antibodies against the human papillomavirus type 1 (HPV-1) were isolated. The monoclonal antibodies detected HPV-1 antigens in frozen sections of HPV-1-induced warts, using immunofluorescence or immunoperoxidase techniques, and they reacted with HPV-1 particles in an immunodiffusion test. The two monoclonal antibodies recognized the major structural viral polypeptide, with a molecular weight of 54 000, and a minor polypeptide, with molecular weight of 76 000, in both the dissociated viral particles and in the wart extracts.

Antibodies, Monoclonal↗
PubMed1984

The search for a culture system for papillomavirus.

Papillomaviruses induce tumors of keratinocytes. Vegetative viral DNA replication and virion assembly are seen in those cells which are in the process of keratinizing or are keratinized. To date, no cell culture system has been developed that permits expression of the complete viral life cycle. Keratinocytes infected in culture may harbor the virus as a stable, replicating episome, but they do not support vegetative viral growth, nor do they become immortalized or transformed. The major obstacle in using keratinocyte cultures may be related to a dual need for transformation and full differentiation. Some animal papillomaviruses have been shown to be capable of transforming cultured murine fibroblasts. The fibroblast model is useful for identifying the viral-transforming gene(s) and their products.

Animals↗
PubMed1978

The human papillomaviruses.

Recent biochemical and serological studies have shown the existence of at least four distinct types of human papillomaviruses (HPVs) causing benign skin lesions. These viruses show hardly no antigenic relationships; their DNAs differ by their sensitivity to restriction endonucleases, and show little, if any, sequence homology, as detected by molecular hybridization using complementary RNAs transcribed in vitro. Data on the pathogenicity of HPVs are still incomplete but indicate that some types of benign skin lesions (plantar warts, common warts, flat warts) may be preferentially associated with some types of HPV. Most interesting is that epidermodysplasia verruciformis has been found associated with two types of virus, and that malignant conversion of some lesions has been observed in all the patients infected with one of them. This suggests that at least a HPV may have a higher oncogenic potential, as do rabbit (Shope) papillomavirus and bovine alimentary tract papillomavirus. Much remains to be known on human papilloma-viruses and further studies may lead to the characterization of additional types of HPVs, especially in genital condylomata acuminata and laryngeal papillomas whose malignant conversion, although rare, may be observed. Progress in this field has been and remains hampered by the lack of cell culture systems allowing replication of these highly host and tissue specific viruses, and by the widely variable virus content of the different human lesions known to be associated with a papillomavirus. Further studies are warranted by the possible role of these widespread and epitheliotropic viruses in the origin of some carcinomas in man.

Cell Transformation, Neoplastic↗
PubMed1977

Chromatin-like structures obtained after alkaline disruption of bovine and human papillomaviruses.

Four low-molecular-weight polypeptides migrating like H2a, H2b, H3, and H4 calf liver histones were detected by sodium dodecyl sulfate-acrylamide gel electrophoresis of highly purified preparations of bovine papillomavirus (BPV) and human papillomavirus (HPV). Complexes of these polypeptides and viral DNA were isolated by agarose-gel filtration of the alkaline disruption products of both viruses. When observed under the electron microscope, these complexes appeared as circular structures composed of nucleosomes with a diameter of about 8.0 nm interconnected by a naked DNA filament. The maximal frequency of nucleosomes per molecule was 30 for both viruses, corresponding to a condensation ratio of the viral DNA of 2.5.

Bovine papillomavirus 1↗