Inhibition of mammalian DNA polymerase by the 5'-triphosphate of 1-beta-d-arabinofuranosylcytosine and the 5'-triphosphate of 9-beta-d-arabinofuranoxyladenine.Summary The 5′-triphosphate of 1-β-d-arabinofuranosylcytosine (ara-CTP) was tested as a substrate or inhibitor of polynucleotide synthesis using mammalian polymerases. The compound did not replace deoxycytidine triphosphate (dCTP) as substrate for DNA polymerase and did not replace cytidine triphosphate as substrate for RNA polymerase. The compound was found to inhibit DNA synthesis catalyzed by DNA polymerase; the inhibition appeared to be competitive with dCTP. No inhibition of RNA polymerase was observed. Further studies indicate that the inhibition of mammalian DNA polymerase by the 5′-triphosphate of 9-β-d-arabinofuranosyladenine (ara-ATP) is also competitive with the corresponding deoxytriphosphate. The data on the mode of action of 1-β-d-arabinofuranosylcytosine and of 9-β-d-arabinofuranosyladenine have been summarized, and the present status of hypotheses on these mechanisms have been discussed. The data are consistent with the view that ara-CTP and ara-ATP act in animal cells via their respective triphosphates to inhibit the animal cell DNA polymerase, although ara-ATP, but not ara-CTP, may also act by inhibiting ribonucleotide reductase.
On the Role of Thymus, Spleen, and Gonads in the Development of Leukemia in a High-Leukemia Stock of MiceThis study explores the possible application of a biodegradable plant based surfactant, obtained from Sapindus mukorossi, for washing low levels of arsenic (As) from an iron (Fe) rich soil. Natural association of As(V) with Fe(III) makes the process difficult. Soapnut solution was compared to anionic surfactant sodium dodecyl sulfate (SDS) in down-flow and a newly introduced suction mode for soil column washing. It was observed that soapnut attained up to 86% efficiency with respect to SDS in removing As. Full factorial design of experiment revealed a very good fit of data. The suction mode generated up to 83 kPa pressure inside column whilst down-flow mode generated a much higher pressure of 214 kPa, thus making the suction mode more efficient. Micellar solubilisation was found to be responsible for As desorption from the soil and it followed 1st order kinetics. Desorption rate coefficient of suction mode was found to be in the range of 0.005 to 0.01, much higher than down-flow mode values. Analysis of the FT-IR data suggested that the soapnut solution did not interact chemically with As, offering an option for reusing the surfactant. Soapnut can be considered as a soil washing agent for removing As even from soil with high Fe content.
Some delayed effects of atom-bomb radiations in mice.Summary 1.Male and female (C57L × A/He)F 1 mice surviving instantaneous exposure to ionizing radiation from an experimental nuclear detonation were observed until natural death for delayed effects of irradiation. 2.Among the effects observed was shortening of the lifespan, which varied with the radiation dose. 3.The shortening of life was not attributable to increased mortality from any specific cause but was correlated with premature onset of all diseases associated with natural senescence. 4.Although the effects of radiation on the incidence and severity of diseases of old age varied markedly from one disease to another, all diseases were advanced in onset to essentially the same extent by any one dose of radiation, with the exception of thymic lymphoma. 5.The onset of thymic lymphoma was hastened considerably more than that of any other disease, particularly in heavily irradiated mice, which also had an elevated incidence of this neoplasm. 6.There was no consistent over-all relation between the frequency of neoplasia and the radiation dose. The incidence of certain neoplasms (thymic lymphoma, adenocarcinoma of mammary gland, pituitary adenoma, adrenal adenoma, Harderian gland adenoma, hepatoma, ovarian tumor, and granulocytic leukemia) was increased by irradiation, whereas the incidence of others (pulmonary adenoma, mammary gland sarcoma, nonthymic lymphoma) was decreased. In no instance was there a linear relation between tumor incidence and dose. Most neoplasms were less common after large doses of radiation than after intermediate doses, suggesting that neoplasia was inhibited by excessive radiation injury. 7.Depigmentation of the hair, which was detected as early as 3 months after irradiation, progressed at a rate and to an extent that varied with the dose, but it was not observed in lightly irradiated mice or in the controls. 8.Cataract of the optic lens, which was also noted within 90 days after irradiation, progressed at a rate and to an extent that varied with dose. The radiation cataracts differed in location from the opacities occurring spontaneously in senile controls. 9.Atrophy of the iris, which developed spontaneously in senescent controls, occurred prematurely in irradiated mice and progressed in severity with the dose. 10.Radiation nephritis, or nephrosclerosis, was common in mice receiving more than 400 rad but was rare below this dose level. In a few mice with advanced nephrosclerosis, polyarteritis was noted in the kidney and elsewhere. 11.Miscellaneous infectious and inflammatory lesions, which were relatively rare in controls, were not increased in frequency by irradiation. 12.Subcapsular ovarian cysts and hydrometra, which were relatively common in aging controls, were reduced in incidence in irradiated females, possibly through sterilization of the ovary. 13.Loss of incisor teeth occurred in a relatively high proportion of aging males and was nearly 10 times as common in males as in females. Its frequency was not significantly affected by irradiation. 14.For most of the effects observed, neutrons were more effective than gamma rays. Because, however, of uncertainties in dosimetry and the relatively small numbers of neutron-exposed animals, precise estimation of the relative effectiveness cannot be made from the results of this experiment.