Irene U. Boone

Volume Distribution and Separation of Normal Human Leucocytes.

Summary Leucocytes from normal adults have been studied by electronic sizing and separating methods. The volume distribution was found to be bimodal. Three cell groups of small volume dispersion were isolated and subsequently identified by hematological methods. The smaller-volume leucocyte peak was found to contain small lymphocytes and little else. The large-volume peak contained granulocytes in its central portion and mono-cytes in its large-volume tail. Using these methods, the relative abundance of a specific type of leucocyte can be greatly increased. These methods may also be applied to other cell suspensions.

Toxicity, metabolism, and tissue distribution of carbon14-labeled N,N′,N″-triethylenethiophosphoramide (Thio-TEPA) in rats☆

Abstract The toxicity, histopathology, tissue distribution, and metabolism of Thio-TEPA were studied following intravenous and intra-arterial injection into adult male Sprague-Dawley rats. The LD 50 30 for all animals injected intravenously or intraarterially with Thio-TEPA was 9.06 ± 0.45 mg per kilogram of body weight. The route of injection did not influence the toxicity and histopathology, nor did it markedly affect the distribution of C 14 activity in the tissues obtained 5 minutes after injection of labeled Thio-TEPA. Fixation of Thio-TEPA in tissues appears to be much slower than fixation of NH2 and resembles that of TEM. At least 95% of the C 14 activity of the drug and its metabolites was excreted in the urine 8 hours after drug injection. Following the intravenous injection of 9.0 mg/kg of Thio-TEPA, 20–30% of the drug was excreted as the metabolite TEPA, while 70–80% of the drug was excreted unchanged. Of the 3 alkylating agents (HN2, TEM, and Thio-TEPA) studied in this laboratory, HN2 would appear to be the drug of choice for local cancer chemotherapy and treatment of cancer by perfusion.

Metabolism of tritium-labeled pyridoxine in rats.

Summary Urine, blood, and fecal samples from rats injected intravenously with tritiumlabeled pyridoxine hydrochloride were collected at various time intervals post injection for excretion and chromatographic study. Approximately 70% of the administered label was excreted in the urine in 5 hours. Fecal excretion was less than 0.03% in 96 hours post injection. There were 2 rates of excretion: the initial rapid rate with a half-time of about 45 minutes, followed by a slower rate with a half-time of 17 days. Chromatographic studies of urine showed that the pyridoxine was excreted primarily unchanged with a small amount of only one metabolite, most likely 4-pyridoxic acid.

Relationship of Pyridoxine and its Derivatives to the Mechanism of Action of Isoniazid.

Summary 1. It was possible to inhibit growth of organisms other than Mycobacterium with isoniazid by controlling the amount of pyridoxine and its derivatives in the media. Lactobacillus plantarum and Saccharomyces carlsbergensis were inhibited in a synthetic medium by isoniazid concentrations of less than 102 M. This inhibition was competitively reversed by pyridoxine, pyridox-amine, and pyridoxal. In reversing isoniazid inhibition of Lactobacillus, pyridoxamine, and pyridoxal were from 1000 to 4000 times more effective, than pyridoxine. 2. Two strains of E. coli were inhibited with isoniazid with partial reversal with pyridoxine and derivatives. Larger amounts of the metabolite were required and the reversal was not as typically competitive. 3. No reversal of isoniazid inhibition could be obtained with vit. B6 or its derivatives in any of the Mycobacteria tested. If isoniazid acts as an antagonist of pyridoxine or its derivatives in the Mycobacteria, it is not a simple substrate competition or uptake phenomenon.

RELATIVE EFFECTIVENESS OF NEUTRONS FOR PRODUCTION OF DELAYED BIOLOGICAL EFFECTS. II. EFFECT OF SINGLE DOSES OF NEUTRONS FROM AN ATOMIC WEAPON ON LIFE SPAN OF MICE

Mice were exposed to neutrons or to mixtures of neutrons and gamma - rays from an atomic detomation and allowed to live out their life span. It was found that neutrons shortened the mean life span by 6.7% per 100 rads, and it was estimated that gamma rays shortened the life span by 2.6% per 100 rads. The relative effectiveness of neutrons for production of this delayed response was 2.6, a value in close agreement with those previously obtained for production of acute effects. (auth)

Toxicity, Excretion and Tissue Distribution of Ionium (Th230) in Rats

The excretion, tissue distribution, and toxicity of ionium (Th/sup 230/ were studied following its intravenous administration in the rat. In addition, separate groups of animals were injected with ionium for histopalhologic and radioautographic tissue studies. The results are summarized. (auth)

Studies with transplantable AK4 mouse leukemia. II. Relative biological effectiveness of thermal neutrons as compared to x-rays.

A variety of end points have been used to determine the relative biological effectiveness (RBE) of radiations having different values of linear energy transfer (LET) in tissue. These studies resulted in a wide range of RBE values, which, when properly interpreted, have contributed to the understanding of radiation effects. The values for RBE of various radiations and their relation to LET have been extensively reviewed recently (1-3). That transplantable tumors of one species or strain of animals may be transplanted to a heterologous species or strain after exposure of the recipient animals to sublethal doses of radiation is well known. The percentage of successful transplants has been shown to be roughly proportional to dose. Furth et al. (4) found that the percentage of mice rendered susceptible by radiation was increased with increasing radiation doses. Using CFW Swiss mice, Werder et al. (5) have shown that the incidence of transplantable Line Ib leukemia varied with radiation dose over the range of 100 to 400 r. In a previous report Boone (6) reported a linear relationship between probit of per cent incidence of transplantable AKR mouse leukemia and log dose after exposure of four highly inbred heterologous strains of mice to 100 to 550 r of X-rays. With the incidence of successful heterologous leukemic implants taken as the end point, the biological effectiveness of thermal neutrons relative to X-rays has been determined in three strains of inbred mice.