Differential effects of selenium on normal and neoplastic canine mammary cells.

Four different canine mammary tumor (CMT) cell lines and a nonneoplastic primary culture of mammary cells were examined for their in vitro responsiveness to selenium supplementation. These cell lines were found to vary in their metabolic response to increasing concentrations of selenium. Sensitivity to selenium, as sodium selenite, increased with increasing concentrations of this trace element in all of the neoplastic lines. These data also suggest that increasing the plating density of tumor cells further increases the sensitivity to selenium. A relatively selenium-sensitive cell line (CMT-13) and relatively insensitive cell line (CMT-11) were characterized on the basis of reduced growth resulting from selenium supplementation. Increasing the concentration of selenium to 0.75 microgram/ml depressed the growth of CMT-13 and CMT-11 cells by 75% and 11%, respectively, while no inhibition was observed in nonneoplastic cells. These cell lines also varied in their sensitivity to different forms of selenium. Selenodiglutathione was the most effective form of selenium examined that inhibited tumor cell growth. The sensitivity of the neoplastic lines was selenodiglutathione much greater than sodium selenite much greater than selenocystine greater than selenomethionine. None of the forms of selenium examined inhibited the growth of the nonneoplastic mammary cells in culture. Supplementation with sodium selenite (1 microgram Se per ml) for 60 min resulted in a dramatic depression in RNA biosynthesis in CMT-13, but not CMT-11 or nonneoplastic cells.

Inhibition of human breast cancer cells by selenium.

The viability of human breast cancer cells (cell lines MCF-7 and MDA-MB 231) was inhibited in vitro in a dose-dependent manner by selenium supplementation. However, a normal diploid human cell line (MRC-5) was relatively resistant to selenium supplementation. The presence of selenium as Na2SeO3 at 1.1 X 10(-6) M reduced cancer cell viability by approximately 50%, whereas non-cancerous cells were not affected. Parenteral administration of sodium selenite also significantly inhibited the growth of the cancerous cell lines transplanted into nude mice. Selenium administration at 0.8 micrograms/g body wt resulted in an 80-93% reduction in the rate of tumor growth without apparent ill effects on the host.

Effect of selenium on growth rate of canine mammary carcinoma cells in athymic nude mice.

A canine mammary tumor cell line established from a carcinoma of the solid type was used in this study. In 2 separate experiments, athymic nude mice were inoculated subcutaneously with 5 x 10(6) viable tumor cells. All tumor-bearing mice received subcutaneous injections thrice weekly of 2 micrograms/g body wt of selenium as sodium selenite or phosphate buffered saline. Control, non-tumor-bearing mice were injected with either selenium or buffer. Selenium administration did not significantly alter the growth of non-tumor-bearing mice. However, body weight of tumor-bearing mice was reduced approximately 10%. The average volume of tumors in selenium treated mice was reduced 76% in experiment I and 74% in experiment II.

Canine papilloma: progression of oral papilloma to carcinoma.

Squamous cell carcinoma was found in association with extensive and progressive oral papillomas in a 1 1/2-year-old male beagle. The neoplasm was in the region of the posterior portion of the right law and evidently originated from the adjacent papillomatous growths. Possible relationship between the duration and extent of papillomatosis and the appearance of malignant change, heretofore not reported, is discussed.

Studies of laryngotracheitis virus in avian tissue cultures. 3. Enhancement of infectivity by diethylaminoethyl-dextran.

Diethylaminoethyl-dextran (DEAE-D) enhanced the infectivity of laryngotracheitis virus (LTV) for chicken kidney (CK) cells when cultures were treated before inoculation with virus and when DEAE-D was present in the inoculum. Infectivity was not increased when cultures were treated after virus had adsorbed to cells; since infection was not synchronized, most of the virus had probably already penetrated the plasma membrane by the time DEAE-D was added. Maximal enhancement occurred when DEAE-D was present in the inoculum. Enhancement of a lesser degree occurred when virus and DEAE-D were mixed, diluted, and inoculated onto cultures. Adsorption of LTV at 37 C as compared to that at 5 C usually yields about a threefold greater number of plaques after a 2-hr adsorption period. However, when DEAE-D was incorporated in the inoculum, greater enhancement occurred at 5 C than at 37 C, and the number of plaques produced at both adsorption temperatures was about equal. Results are compatible with the hypothesis that increased adsorption is a factor in enhancement of infectivity of LTV by DEAE-D.

Serological, biochemical and structural properties of three bovine picornaviruses.

Three viral agents isolated from nasal exudate of Illinois cattle affected with respiratory disease were studied. The agents were classified as picornaviruses on the basis of their resistance to ether, stability at pH 3.0, and morphological characteristics. Magnesium chloride at 1 M concentration protected the viruses from reduction of infectivity by exposure to 50 degrees C for one and two hours. None of the viruses was pathogenic for mice. Replication of one of the viruses was not affected by the DNA inhibitor, 5 fluorodeoxyuridine. That two of the agents were closely related serologically was demonstrated by serum neutralization tests. As revealed by electron microscopy, viral particles were spherical or hexagonal and ranged in size from 280 A to 290 A.