PubMed Health⌕ Search

Biomedical subjects

B Mintz

Publications and source records attributed to B Mintz.

At least 91 records · Page 5Linked to original sources

Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA.

Explanted mouse blastocysts were microinjected in the blastocoel cavity with simian virus 40 (SV40) viral DNA. After surgical transfer to the uteri of pseudopregnant surrogate mothers, approximately 40% of the blastocysts developed to term and became healthy adults without apparent tumors at 1 year of age. Molecular hybridization tests for the presence of SV40-specific DNA sequences were conducted on DNA extracted from various organs of these animals. Between 0.5 and 13 SV40 genome equivalents per diploid mouse DNA value were found in some organs of approximately 40% of the adult survivors; this represents a substantial augmentation of the amount administered per embryo. The results are consistent with the working hypothesis that the SV40 DNA may have been integrated into the host genome; alternatively, the viral DNA may have replicated as an extrachromosomal entity or by lytic infection in a few permissive cells. Persistence of the viral DNA from preimplantation stages to adult life may thus provide a new tool for experimental investigation of vertical transmission and expression of tumor viruses.

Animals↗

Contact-mediated myogenesis and increased acetylcholinesterase activity in primary cultures of mouse teratocarcinoma cells.

Transplantable mouse teratomas are known to contain multipotential teratocarcinoma stem cells analogous to early embryo cells and capable of giving rise to a wide variety of specialized cell types in vivo when they attach to a substratum; if they are grown instead in suspension in the body cavity, they form multicellular embryoid bodies which proliferate with little or no cell specialization. Thus, changes initiated at the cell surface may play some role in promoting early cell differentiation. In order to establish an in vitro system for experimental investigation of this hypothesis, embryoid body cells were explanted under conditions of cell attachment versus suspension and maintained in primary culture. Because cell differentiation in previous reports was relatively limited in vitro, the two cellular populations were first compared for genesis of a quantifiable macromolecular phenotype, acetylcholinesterase (AChE) activity, which characterizes several of the cell types most commonly formed in the attached tumors in vivo. The attached cells produced markedly increased levels of AChE activity within a few weeks, while cells in suspension retained basal levels. AChE was histochemically visualized and was found to occur chiefly in cells undergoing myogenesis, especially during myotube formation. Aberrant muscle fibers formed and became predominant in the cultures. When embryoid bodies were first fractionated by increasing size, which reflects their progressive differentiation, the smallest ones, with relatively more multipotential cells and no apparent muscle cells, also showed AChE increase in attached cultures. The results are consistent with the view that attachment of the cell surface to a substratum may play a critical role in initiating some cellular developmental commitments, as well as in sustaining differentiation of cells whose specialization has already been determined. Further experimental modifications of this primary culture system of teratocarcinoma cells should be useful in analyzing cell-substratum relations and cell-surface changes in early mammalian development.

Acetylcholinesterase↗

Change in cell-surface glycoproteins of mouse embryos before implantation.

The early biochemical ontogeny of the mammalian cell surface has been examined in mouse embryos. After in vitro incubation of embryos in D-[(3)H]- or D-[(14)C]glucosamine, the cell-surface glycopeptides were removed by trypsinization, digested with Pronase, and fractionated by gel filtration on Sephadex G-50; radioactivity was determined in the fractions by scintillation counting. Cochromatography of digests from the surfaces of embryos of two age groups yielded markedly different elution patterns. The labeled surface material from embryos in or near the blastocyst stage, when the outermost cells are differentiating into trophoblast, was substantially enriched, as compared with material from cleavage-stage embryos, in relatively more rapidly eluted components of presumed higher molecular weight. A similar change has previously been reported by others in cultured mammalian cell lines after viral transformation, in comparison with corresponding untransformed cells. This similarity between blastocysts and transformed cells suggests that the early biochemical differentiation of the surface, as the embryo passes into the blastocyst stage, may be responsible for the stage-specific capacity of the outermost cells to attach to the uterine wall in response to an implantation-initiating stimulus and to become invasive.

Animals↗

Seminal vesicle formation and specific male protein secretion by female cells in allophenic mice.

The relation of cellular sex genotype to phenotype was examined in seminal vesicles of adult allophenic mice with cellular sex chromosome mosaicism. Each animal originated from conjoined blastomeres of an embryo of female (XX) and one of male (XY) constitution, from different inbred strains. Cells of both sexes were detected in bone marrow and certain other somatic tissues; cellular sex of seminal vesicles was deduced from strain-associated electrophoretic variants of proteins coded for at autosomal loci. Seminal vesicles composed partly or entirely of female cells were found in male and pseudohermaphrodite individuals. In a pseudohermaphrodite, both allelic variants of the tissue-specific normal male seminal vesicle protein (Svp-locus) were present, signifying that female as well as male cells were synthesizing the protein. Male-determining factors on the Y chromosome are thus not required in cells that differentiate into functional seminal vesicles.

Animals↗

Pure-strain and genetically mosaic liver tumors histochemically identified with the -glucuronidase marker in allophenic mice.

A histochemical procedure for beta-glucuronidase has been used to make visible the cellular genotypes of liver tumors and of surrounding normal liver clones in allophenic mice. The animals had lifelong genetic mosaicism for cells with the allele for low beta-glucuronidase activity (g/g genotype, C3H strain) and cells with the allele for high activity (G/G genotype, C57BL/6 or BALB/c strain). The former strain is also hepatoma-susceptible; both the latter are nonsusceptible. Of 12 "spontaneous" hepatomas examined, nine were entirely of susceptible-strain hepatic cells and one was of the nonsusceptible strain; the pure-strain tumors usually arose in a liver environment containing clones of each genotype. The cells therefore behave largely autonomously with respect to gene control of tumor susceptibility. However, two tumors with malignant cells of both genotypes were formed, which suggests some measure of intercellular transmission of tumor information. Alternatively, transformation might have occurred in two or more cells concurrently. Mosaic tumors in either case imply that even a hepatoma of one inbred strain, whether in a single-genotype animal or an allophenic mouse, may comprise diverse clones of transformed cells. Possibly many or all hepatomas may therefore be genetically complex entities.

Animals↗