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K S Sastry

Publications and source records attributed to K S Sastry.

At least 37 records · Page 2Linked to original sources

Intracellular distribution and radiotoxicity of chromium-51 in mammalian cells: Auger-electron dosimetry.

The kinetics of uptake and of radiotoxicity of chromium-51, an Auger-electron emitter, have been studied in V79 lung fibroblasts of the Chinese hamster. Intracellular radioactivity was directly proportional to the incubation period and to the extracellular concentration of the Cr-51. About 14% of the cellular activity was associated with the nucleus, whereas approximately 2% was guanidine-precipitable and therefore bound to DNA. The growth rate of V79 cells was slowed following intracellular incorporation of Cr-51. The cell-survival curve, in terms of colony-forming ability, was of the low-LET type, with a D37 of 6.2 pCi/cell. Theoretical dosimetric estimates indicate that, under the given experimental conditions, the mean lethal dose to the cell nucleus was 870 rad. Although this value is somewhat larger than the x-ray D37 dose of 580 rad for this cell line, it is more realistic than the gross underestimate obtained by classical MIRD calculations (2-3 rad/cell).

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In vivo effects of iron-55 and iron-59 on mouse testes: biophysical dosimetry of Auger electrons.

When the Auger-electron emitter, 55Fe, and the beta-emitter, 59Fe, are similarly distributed in the testes of mice, the conventionally calculated average radiation dose to the organ from 55Fe is about 2.6 times more effective in reducing the sperm-head count than the dose from 59Fe. This finding emphasizes the ability of low-energy Auger electrons to damage radiosensitive targets of cells through localized irradiation. The observed efficacy is understandable in terms of dosimetric models based on intracellular distribution studies of the radionuclides.

Animals↗

Thallium-201: an experimental and a theoretical radiobiological approach to dosimetry.

The kinetics of uptake and retention of Tl-201, Rb-86, and K-42 and -43 have been studied in cultured mammalian cells and related to their radiotoxicities. Among the four radionuclides, the intracellular localization of Tl-201, the only emitter of Auger electrons, was important for the manifestation of its cytocidal effects. The results have been found consistent with the short-range nature of Auger electrons and are substantiated by our theoretical dosimetric calculations. The possible implications of this in vitro system for applications of Tl-201 in nuclear medicine are indicated.

Animals↗

Radiotoxicity of thallium-201 in mouse testes: inadequacy of conventional dosimetry.

When TI-201 is concentrated in mouse testes, the low-energy Auger electrons following its electron-capture decay are found to be much more effective in causing loss of testicular weight and reduction of sperm heads than the energetic beta particles from similarly distributed TI-204. These results are contrary to expectations based on conventional dosimetry of tissue-incorporated radionuclides, and point to possible underestimation of risks by the currently adopted dosimetric procedures, especially in the case of radionuclides decaying by electron capture and internal conversion.

Animals↗

Effects of early diabetes on uridine diphosphosugar synthesis in the rat renal cortex.

To assess the effects of streptozotocin-induced diabetes on the substrates utilized in the formation of glycoproteins, the pools of uridine 5'-diphosphoglucose (UDPG), uridine 5'-diphosphogalactose (UDP-GAL), uridine 5'-diphosphoglucuronic acid (UDPGA), and uridine 5'-diphospho N-acetyl galactosamine (UDPA-GAL) were measured in the renal cortex of control and over a 48-hr period in diabetic rats. In control rats these pools measured: UDPG, 256 +/- 23; UDP-GAL, 75 +/- 14; UDPGA, 147 +/- 16; UDPAG, 367 +/- 23; UDPG-GAL, 131 +/- 13 nmoles/mg DNA. In diabetic rats, except for UDP-GAL, all pools were increased 41 to 68%. The incorporation of radiolabeled orotate was increased in all pools, except UDP-GAL, in diabetic rats by 41 to 77% compared to control rats. The incorporation into UDPG and UDPAG was increased even after correction for the specific radioactivity of their immediate precursor, uridine 5'-triphosphate (UTP). Expansion of the UTP pool after orotate infusion was associated with an increase in the size of the UDPG and UDPAG pools in both control and diabetic rats. Depletion of the UTP pool after adenine infusion in controls was associated with a decrease in all pools. This study demonstrates that after the induction of diabetes there is a rapid increase in the bioavailability of substrates utilized in the synthesis of glycoproteins and glycosaminoglycans. It is theorized that this increase is necessary for the augmented synthesis of basement membrane-like material in the diabetic kidney.

Animals↗

Intracellular potassium: 40K as a primordial gene irradiator.

We have been interested in the possibility that the low energy electrons (Auger and Coster-Kronig) emitted after the electron capture decay of 40K may have highly localized radiochemical effects on the genetic material--effects dependent upon the intracellular locus of potassium. We report here that these effects are such that the likelihood of mutagenesis by their impact on DNA is substantial. This suggests that intracellular 40K has played a significant role as a mutagenic agent in evolution.

Animals↗

Alterations in glomerular RNA in diabetic rats: roles of glucagon and insulin.

Incorporation in vivo of labeled orotate into RNA and total nucleotides was measured in isolated glomeruli and whole renal cortex. In 2-day diabetic animals, glomerular RNA was increased, and there was greater incorporation of orotate into total nucleotides and RNA as compared with controls. Insulin reversed the exaggerated incorporation at infusion rates that corrected hyperglucagonemia without reducing plasma glucose and with only minimal changes in insulin concentrations. The addition of glucagon to insulin infusions reproduced the increased incorporation observed in untreated diabetics. Similar changes occurred in renal cortex, where differences in orotate incorporation into nucleotide precursors seemed to be the main cause for alterations in RNA labeling. Isotope incorporation in glomeruli correlated positively with plasma glucagon, but not with insulin or glucose concentrations. Although in 7-month diabetic animals orotate incorporation into RNA was less than in controls, probably as a consequence of renal disease, 24-hour insulin infusion decreased it further. Our results confirm that in the diabetic kidney, abnormal uracil nucleotide metabolism and increased cellular content of RNA are demonstrable in glomeruli as in the renal cortex. These changes appear to be related directly to hyperglucagonemia.

Adenine↗

Interrelationships in trace-element metabolism in metal toxicities in a cobalt-resistant strain of Neurospora crassa.

A strain of Neurospora crassa was isolated by training the mould to grow on media containing high concentrations of Co(2+). This strain, the Co(R) strain, exhibited approximately tenfold the resistance of the parent strain to Co(2+) and Ni(2+) but not to Zn(2+) or Cu(2+). Co(2+) toxicity in the Co(R) strain was reversed by Mg(2+) but not by Fe(3+). Also, Co(2+) did not affect iron metabolism in this strain. It is suggested that the mechanism of resistance in the Co(R) strain involves an alteration in the pattern of iron metabolism such that the latter is no longer adversely affected by toxic concentrations of Co(2+). The Co(R) strain is genetically stable and is most probably a result of a resistance mutation in N. crassa induced by Co(2+).

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