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Biomedical subjects

A C Davies

Publications and source records attributed to A C Davies.

11 recordsLinked to original sources

Isolation and properties of rat cell lines morphologically intermediate between cultured mammary epithelial and myoepithelial-like cells.

The cloned cuboidal epithelial cell line Rat Mammary (Rama) 25 converts at low frequency in culture to elongated cells that possess some of the properties of myoepithelial cells; one such clonal cell line is termed Rama 29. Three morphologically intermediate clonal cell lines have been isolated from Rama 25 which form a morphological series in the order: Rama 25 cuboidal cells, Rama 25-Intermediate 2(I2), Rama 25-I1, Rama 25-I4, and Rama 29 elongated cells. This same order is largely maintained for increasing percentages of elongated cells, decreasing percentages of cuboidal cells, decreasing tubular structures on collagen gels, and increasing times of appearance of tumors in nude mice. The fully elongated cells fail to revert to cuboidal cells and to form tumors. Binding of antisera to epithelial-specific milk fat globule membranes and human keratin declines whereas binding of antisera to myoepithelial-associated laminin, vimentin, and Thy-1 increases in the cell lines in the same order. Similarly 7 polypeptides characteristic of elongated cells increase and 4 polypeptides characteristic of cuboidal cells decrease in the cell lines in the same way. Anti-actin serum binds equally to all cell lines grown on plastic, except for Rama 25-I4, where its binding is increased. Rama 25-I1 and Rama 25-I4 cells also give rise to anti-actin, anti-myoglobin, and phosphotungstic acid hematoxylin-staining giant, striated cells on collagen gels and in tumors that also have ultrastructural characteristics of skeletal muscle. Fresh elongated converts of Rama 25 bind appreciably more anti-actin serum than many of the clonal elongated cell lines such as Rama 29. Ultrastructural analysis confirms the gradual loss of epithelial characteristics and the acquisition of immature myoepithelial characteristics in the same sequence of cell lines. It is suggested that such a linear sequence of intermediate morphological states occurs between the Rama 25 cuboidal cells and the elongated myoepithelial-like cells in vitro, and that a similar morphological sequence may exist in terminal ductal structures in vivo.

Actins

The use of a low-osmolality contrast medium in hysterosalpingography: comparison with a conventional contrast medium.

Hexabrix 320 has been compared with Conray 280 in a randomised double-blind study of 97 patients undergoing hysterosalpingography. Although the lower osmolality and higher viscosity of Hexabrix should make it an ideal hysterosalpingographic agent, no differences were detected between the two contrast media, either in the incidence of side-effects or in radiographic image quality.

Abdomen

A comparison of the phototumorigenic potential of 8-MOP and 5-MOP in hairless albino mice exposed to solar simulated radiation.

Hairless albino mice have been treated with topically applied 8-methoxypsoralen and 5-methoxypsoralen at two concentrations and exposed to solar simulated radiation. Both these compounds significantly increased the incidence of cutaneous tumours when compared with controls irradiated after treatment with vehicle. This effect was related to psoralen concentration and at the two concentrations investigated there was no significant difference between the compounds.

5-Methoxypsoralen

Immunocytochemical demonstration of hormonally regulable casein in tumors produced by a rat mammary stem cell line.

The rat mammary epithelial stem cell line, Rat Mammary 25, and the dimethyl sulfoxide-resistant variant derived from it, Rama 259, when injected separately into female, virgin, athymic nude mice formed tumors which grew at approximately the same rate. When the mice were mated, the growth rate of the Rama 259 tumors increased 2.5-fold during late pregnancy and lactation, while that of the Rama 25 tumors was unaffected. The tumors in all cases consisted of glandular-like structures and blocks of cuboidal and elongated cells. Antibodies were raised against the three major caseins in rat milk. Examination of histological sections showed that antibodies immunocytochemically stained some of the cells (5 to 20%) in the glandular regions, a few (1 to 5%) of the cuboidal cells, and none of the elongated cells in Rama 25 tumors from lactating mice. Only a relative few (1 to 5%) of the glandular cells stained in Rama 25 tumors from perphenazine-treated mice, while no cells (less than 1%) stained in tumors from virgin mice. The casein antibodies failed to stain any cells (less than 1%) in the Rama 259 tumors even when they stained luminal epithelial cells in the mammary glands taken from the same lactating or perphenazine-treated mice. These results demonstrated that a minor population of cells within the Rama 25 tumors can be hormonally regulated to produce casein in a way similar to that for the majority of the cells in normal mammary glands.

Animals

Retinoid-specific induction of differentiation and reduction of the DNA synthesis rate and tumor-forming ability of a stem cell line from a rat mammary tumor.

Differentiation of the stem cell line rat mammary (Rama) 25 to alveolar-like cells can be monitored by the increase in production of domes (hemispheric blisters) in the cell monolayer and immunoreactive casein in the tissue culture medium. This step was accelerated not only by the synthetic inducer dimethyl sulfoxide (DMSO) but also by all-trans-retinol, all-trans-retinal, all-trans-retinoic acid (RA), and all-trans-retinyl acetate (concentration range, 0.04-4 microM) in the presence of the hormones prolactin, hydrocortisone (HC), insulin, and 17 beta-estradiol; 9-cis-all-trans-retinal was without effect. A combination of RA and HC was active in producing doming, whereas RA, all four hormones, and serum were required for maximum production of immunoreactive casein. The retinoids in the same concentration range also caused a reduction in the DNA synthetic rate in a similar time period. When Rama 25 cells were treated with RA and the four hormones yielding the droplet and doming cultures, subsequent injection of these cells into young, female inbred nu/nu (nude) mice led to a reduced incidence of tumors compared with injections of untreated cells. Tumorigenic variant cell lines were selected previously from Rama 25 that were either elongated and failed to differentiate at all to doming and casein-secreting cultures (Rama 521) or that did so spontaneously but whose rates were not accelerated by addition of DMSO (Rama 259). Both Rama 521 and Rama 259 failed to respond to the retinoids and hormones in producing domes and immunoreactive casein, in decreasing DNA synthetic rates, and in lowering the incidence of tumors induced by injection of the cell lines into nude mice. Thus the anticancer activity of the retinoids in rat mammary gland carcinogenesis may be due in part to their differentiation-inducing properties.

Animals