Marie M. Grenan

LIGHT‐INDUCED LEAKAGE OF SPIN LABEL MARKER FROM LIPOSOMES IN THE PRESENCE OF PHOTOTOXIC PHENOTHIAZINES

Abstract— Liposomes prepared from dipalmitoyl lecithin, cholesterol and dicetyl phosphate and containing a trapped spin label marker were exposed to long wavelength UV light in the presence of a series of phenothiazine tranquilizers. EPR spectroscopy was used to detect spin label marker released from liposomes, taking advantage of the disappearance of line broadening from electron spin exchange which occurred on spin label release. The minimum effective phototoxic dose in mice of these phenothiazines was also determined. Kinetic studies of light‐induced spin label release from phenothiazine‐sensitized liposomes showed that membrane damage was rapidly induced and that the damaging species were short‐lived. The damage process was oxygen dependent and could be temporarily prevented by cysteamine or α‐tocopherol added immediately before irradiation. Only those phenothiazines which mediated light‐dependent liposomal membrane damage had phototoxic activity in mice and the degree of photosensitization was parallel in the two systems. In both photosensitization phenomena, the nature of the substituent at the phenothiazine 2‐position was more important than the phenothiazine side chain.

Radioprotection by mitotic inhibitors and mercaptoethylamine.

In the mouse, chemical interference with cellular proliferation alters the radiosensitivity of the bone marrow, and this results in protection from otherwise lethal x-irradiation. When intestinal damage is minimized by appropriate timing and dosage, many mitotic inhibitors increase radioresistance and enhance the protective effects of mercaptoethylamine.

Mouse Endogenous Spleen Counts as a Means of Screening for Anti-Radiation Drugs

Abstract Using eight radioprotective compounds, a comparison was made between the “standard” survival method and a method employing the counting of macroscopic spleen colonies in assessing the degree of radioprotection. The two methods yielded similar assessments of the degree of radioprotection afforded and required about the same amount of man-hours to conduct the procedure. The spleen colony method offers the advantage of completing the assessment after 10 days rather than 30 and yielding fresh tissues from all scored test animals. The use of a system in which macroscopic spleen colonies are counted offers an alternative to employing the method of animal survival in the quantitative assessment of compounds for radioprotective activity.

Structure-Function Studies of the Aminothiol Radioprotectants. Effect of Carbon Chain Length in Mercaptoethylamine Homologs: Mammalian Radioprotection

The relation between chemical structure and radiation protection in mice has been studied for a series of aminothiols. The aminothiols used in this study were β-mercaptoethylamine (MEA) and its pro...

Hexachlorophene as a topically applied chemical for prophylaxis against Schistosoma mansoni infections in mice

Treatment of mouse tail skins with hexachlorophene (1.25% w/v) in absolute methanol or 70% isopropanol suppressed Schistosoma mansoni infections by more than 95% even when the application was performed up to three days prior to exposure to cercarial suspensions by tail immersion. Treatment with concentrations of 0.313% or higher one day prior to exposure provided at least 98% protection when the treated surface was not subjected to water washes of greater duration than 1/2 hour. Tail immersion application of 1.25% hexachlorophene one day prior to exposure still provided 87-92% protection after 3 hours water wash. Wipe application of 1.25% hexachlorophene three days prior to exposure still provided 93% protection following 3 hours water wash. High cercarial recoveries from exposure tubes at the end of exposure periods indicated high antipenetrant activity for hexachlorophene. Sufficient hexachlorophene leached from treated tail skins into the surrounding water to affect subsequently added cercariae so that they were no longer infective to untreated mice.

Radioprotection by Pressor Amidines

In the mouse, radioprotection is not always associated with the effect of hypertensive amidines and related amines. The protection resulting from this group of agents follows the pharmacological reduction of intercellular oxygen tension. oxygen tension of radiosensitive tissues.

Hemolysin Formation in Mice Following Partial, Total Splenectomy or Spleen Transplantation

Summary Serum hemolysin titers were correlated with weight of remnant spleen present in groups of partially splenectomized NIH mice sacrificed 5 days after intravenous immunization with sheep erythrocytes. Total splenectomy of mice completely suppressed hemolysin formation after intravenous immunization and was associated with a 27% decrease in amount of antibody formed, and a 24 hour delay required for development of peak serum titer. Complete suppression of antibody formation was partially reversed by autologous spleen transplants in splenectomized mice of 2 strains; by isologous transplants in Balb/c but not in NIH mice; and unaffected by homologous transplants in either of the 2 strains.

Antibody production in mice exposed intermittently to radium gamma rays.

Summary Exposure of groups of mice to a radium source providing 8.8 r or 2.2 r per 8 hour day for 51 days resulted in significantly lowered antibody titers. In these experiments the mice were immunized on the third day after the end of the radiation exposure and the serums were sampled on the 5th day after immunization. Antibody titers and leucocyte counts following a single exposure of the mice to an acute X-ray dose 4 days after the end of an intermittent exposure to 450 r of radium gamma rays provided no evidence that the prior exposure produced an altered radiation sensitivity to either the hematopoietic process or the process of hemolysin production. The possibility that antibody synthesis in response to sheep erythrocyte antigen and leucocyte production are independent processes during the recovery from irradiation is discussed.

Effects of Glutathione and Thioglycollic Acid on Acid-Production by Lactobacillus arabinosus in Presence of Atabrine

Summary Under the conditions of these experiments glutathione and thioglycollic acid are capable of reversing the growth inhibiting effect of atabrine on the Lactobacillus arabinosus. Once the concentration of atabrine for complete inhibition had been significantly exceeded, no reversal of bac-teriostasis was attained by increased concentration of glutathione and thioglycollic acid. Several additional compounds were tested under comparable conditions with negative results.