Effects of essential divalent metals on carcinogenicity and metabolism of nickel and cadmium

Interactions between the physiologically essential metals calcium, magnesium, and zinc and the carcinogenic metals nickel and cadmium were investigated to help elucidate the mechanisms of action of the carcinogenic metals. Bioassay studies revealed several significant findings, including: (1) the ability of magnesium and calcium to inhibit nickel-induced elevation of pulmonary adenoma incidence in strain A mice; (2) the ability of magnesium, but not of calcium, to prevent cadmium-induced subcutaneous sarcoma formation; and (3) the ability of magnesium, but not of calcium, to inhibit nickel-induced muscle tumor formation. Biochemical studies indicated a direct relationship between the antitumorigenic potential of magnesium and the capacity of this metal to: (1) inhibit nickel and cadmium uptake by the target tissues in vivo; (2) inhibit nickel-induced disturbances in DNA synthesis in vivo; (3) inhibit nuclear and cytosolic uptake of nickel by the target tissue cells in vivo; and (4) inhibit nickel and cadmium binding to DNA in vitro. Calcium, which in most cases did not prevent carcinogenesis, had no consistent influence on the uptake of carcinogenic metals or their biochemical effects in the target tissues. Magnesium and zinc, but not calcium, were also found to attenuate the acute toxic effects of nickel, indicating a possible correlation between prevention of acute effects and reduction in tumorigenicity. Zinc, which antagonizes cadmium tumorigenicity in the rat testis, was found to reduce markedly cadmium uptake into isolated testicular interstitial cells. Also, zinc was found to inhibit strongly cadmium binding to DNA in vitro.     

Nitrogen mineralization ofSesbania sesban used as green manure for lowland rice in Sri Lanka

Sesbania sesban was evaluated as green manure crop for lowland rice in the Dry Zone of Sri Lanka. The legume was grown during a fallow period before lowland rice (Oryza sativa) and ploughed under just before transplanting. Weight loss and nitrogen content in litterbags containing leaves, stems and roots of the legume were monitored. Comparisons were made between rice yields from 20 m² plots after green manuring in combination with different nitrogen fertilizer levels (0, 2.4, 4.8 and 7.2 gm⁻²) and nitrogen fertilizer (9.6 gm⁻²) alone. Above-ground biomass ofS. sesban was 440 gm⁻² (dry wt) when ploughed under after 84 days growth. N-content in leaves, stems and roots was 3.76%, 0.41% and 0.73%, respectively. This gave a N-input fromS. sesban of 9.2 gm⁻² (8.3 g from above-ground parts and 0.9 g from roots). The corresponding K and P inputs were 7.3 and 0.6 gm⁻² respectively. The nitrogen rich leaves, which contained 88% of the nitrogen in the above-ground parts, decomposed and released its nitrogen much more rapidly than the stems and roots. After only four days the leaves had released 5.3 g Nm⁻² and after 14 days they had released 6.4 g Nm⁻². The highest rice yield (505 gm⁻²) was obtained usingS. sesban and 4.8 gm⁻² of N-fertilizer. The yields with only N-fertilizer or onlyS. sesban were 442 gm⁻² and 396 gm⁻², respectively. Due to the rapid decomposition of the nitrogen rich leaves,S. sesban did not behave as a slow release fertilizer. Thus, it is not necessary to apply nitrogen fertilizers as a basal dose.     

Hybridization of DNA from methanogenic bacteria with nitrogenase structural genes (nifHDK)

Summary Using the Southern hybridization technique, homologies were examined between restricted DNA of four methanogenic bacteria (Methanobacterium ivanovi, Methanobacterium thermoautotrophicum, Methanococcus voltae, Methanosarcina barkeri) and the nif (nitrogen fixation) genes of Klebsiella pneumoniae and Anabaena strain 7120. With K. pneumoniae probes, no hybridization was observed with nifA, nifNE, and nifJ but positive results were obtained with the nifHDK genes coding for nitrogenase. Homology was detected, in the four strains, with K. pneumoniae and Anabaena nifH probes. In M. voltae and M. ivanovi, the homology found with nifH was estimated to be about 70% and a weaker hybridization was observed also with nifD and nifK. In M. voltae, the sequence homologous to nifH was found on a 3.0 kbp HindIII fragment and sequences homologous to nifD and nifK on a 3.8 kbp HindIII fragment. The 3.0 kbp fragment was cloned and the region homologous to nifH was localized more precisely. When this fragment was used as a probe against other DNAs, it behaved as a K. pneumoniae and Anabaena nifH probe. The results suggest that the structural genes for nitrogenase may be present in archaebacteria and raise interesting questions regarding their evolution.     

Chicken erythrocyte membranes: comparison of nuclear and plasma membranes from adults and embryos

These experiments were designed to determine whether the migration of RNA molecules from an implanted nucleus to the host cytoplasm and from there into the host cell nucleus against a concentration gradient might reflect an artefact induced by the process of nuclear transplantation. That is, are RNA molecules, as previously shown for certain nuclear proteins, caused to artefactually leave a manipulated nucleus and then move into the host cell nucleus (as well as return to the grafted nucleus) during the recovery period?A variety of experiments involving different kinds of manipulative sequences and different numbers of nuclear transplantations suggest—but do not prove—that no artefact is involved in the migration of RNA from one nucleus to another but two experiments strongly support the view that the shuttling activity is a normal physiological process. One of the latter involved a determination of the rate of egress of ³H-RNA from an implanted nucleus and reveals that that rate, in contrast with the equivalent rate of egress for labeled proteins which is clearly abnormal after micromanipulation, is totally consonant with the rate of movement of RNA from nucleus to cytoplasm established from experiments that do not involve micromanipulation. The other experiment involves comparison of (1) the amount of radioactivity acquired by an unlabeled nucleus present in the cell at the time a labeled nucleus is implanted with (2) the amount of radioactivity acquired by an unlabeled nucleus implanted after a labeled nucleus had been implanted and had time to recover from any possible operation-induced trauma. With ³H-protein nuclei the host nuclei of (1) acquired much more label than the host nuclei of (2) because in (1) the host nuclei were able to acquire much of the artefactually-released ³H-protein. For the ³H-RNA experiments, however, little difference was found between (1) and (2) in the amount of label acquired by the host cell nuclei. It can be concluded that little, if any, of the non-random shuttling activity of RNA molecules can be a reflection of an artefact.     

Structural Aspects of Saltatory Particle Movement

A variety of cells possess particles which show movements statistically different from Brownian movements. They are characterized by discontinuous jumps of 2–30 µ at velocities of 0.5–5 µ/sec or more. A detailed analysis of these saltatory, jumplike movements makes it most likely that they are caused by transmission of force to the particles by a fiber system in the cell outside of the particle itself. Work with isolated droplets of cytoplasm from algae demonstrates a set of fibers involved in both cytoplasmic streaming and saltatory motion, suggesting that both phenomena are related to the same force-generating set of fibers. Analysis of a variety of systems in which streaming and/or saltatory movement occurs reveals two types of fiber systems spatially correlated with the movement, microtubules and 50 A microfilaments. The fibers in Nitella (alga) are of the microfilament type. In other systems (melanocyte processes, mitotic apparatus, nerve axons) microtubules occur. A suggestion is made, based on work on cilia, that a microtubule-microfilament complex may be present in those cases in which only microtubules appear to be present, with the microfilament closely associated with or buried in the microtubule wall. If so, then microfilaments, structurally similar to smooth muscle filaments, may be a force-generating element in a very wide variety of saltatory and streaming phenomena.     

GABA receptors in Deiters nucleus modulate posturokinetic responses to cortical stimulation in the cat.

The early component of the postural responses which accompany the limb flexion during unilateral stimulation of the motor cortex in the cat is not of reflex origin, but results from a central command. These postural adjustments are characterized by a decreased force under the limb diagonally opposite to the moving one and an increased force under the other two. Since the lateral vestibular nucleus (LVN) exerts an excitatory influence on ipsilateral limb extensor motoneurons, experiments were performed in cats to establish whether the cortical-induced postural changes were mediated through the LVN. This structure is tonically inhibited by GABAergic synapses originating from Purkinje cells of the cerebellar vermis, so that local microinjection into the LVN of GABA agonists or antagonists should either decrease or increase the spontaneous discharge of their neurons. Unilateral microinjection of 0.25 microliters of the GABA-A agonist muscimol or the GABA-B agonist baclofen (at 2-4 micrograms/microliters saline) into the LVN produced a short-lasting episode of ipsilateral postural hypotonia and contralateral hypertonia, during which the cats were unable to stand on the measurement platform. When, shortly after, some recovery of the postural activity appeared, no changes in threshold, latency or amplitude of the cortical-induced flexion movement were observed; however, the early component of the postural responses decreased in the other three limbs. Moreover, the slope of the response curve of the moving limb remained unmodified, while that of the early component of the postural responses, which involved the remaining limbs, decreased following stimulation of the motor cortex at different stimulus intensities. These effects started a few min after the injection and lasted for about 2-3 h. The effects described above were dose-dependent. Moreover, histological controls indicated that the structure responsible for these postural changes corresponded to the middle part of the LVN. The specificity of the results was shown by the fact that unilateral microinjection of 0.25 microliters of the GABA-A antagonist bicuculline or the GABA-B antagonist phaclofen (at 5-8 micrograms/microliter saline) into the LVN produced a postural asymmetry opposite in sign to that elicited in the same experiments by the corresponding agonists. These injections did not modify the amplitude of the cortical-induced limb flexion, but rather enhanced the amplitude of the early component of the postural responses in the other three limbs.(ABSTRACT TRUNCATED AT 400 WORDS)