Biomedical subjects

P A Kitos

Publications and source records attributed to P A Kitos.

At least 37 records · Page 2Linked to original sources

PubMed1985

Effects of diazinon on nucleotide and amino acid contents of chick embryos. Teratogenic considerations.

The effects of diazinon (DZN), an organophosphorus (OP) insecticide, and nicotinamide (Nam) on the pyridine nucleotide, purine and pyrimidine ribonucleotides, and free alpha amino acid contents of chick embryos were determined. The teratogen (DZN) and/or the anti-teratogen (Nam) were administered by the intravitelline route to chicken eggs at day 3 of incubation, and nucleotide and amino acid analyses were made on acid-soluble extracts of homogenates of the embryos at day 10. The results show that the amounts of both the oxidized and reduced forms of NAD and NADP were decreased by the insecticide and restored by Nam. The amounts of the purine and pyrimidine ribonucleotides in the embryos were also decreased by DZN but their changes were proportionately not as great as those of the pyridine nucleotides. The levels of the purine and pyrimidine ribonucleotides were also wholly or partially restored by Nam. Neither DZN nor Nam had any effect on the "energy charge" of the embryos. The levels of free tryptophan (TRP) and histidine (HIS) were decreased by DZN while the levels of threonine (THR) and aspartic acid (ASP) were increased. All other amino acid levels remained virtually unchanged in response to DZN or Nam. Based upon these findings, a possible involvement of TRP in OP insecticide-induced micromelia, parrot beak, and abnormal feathering in chick embryos is considered.

Abnormalities, Drug-Induced↗

PubMed1985

Effects of phosphatase inhibitors on nuclease activity.

Nucleases such as DNase I, which selectively digest chromatin, are inhibited by several commonly used phosphatase inhibitors including sodium bisulfite. Two inhibitors, sodium arsenate and fructose-1,6-diphosphate, did not significantly inhibit nuclease action. Two other effective phosphatase inhibitors, p-chloromercuriphenyl sulfonate and 5,5'-dithiobis(2-nitrobenzoate), can be used during nuclei isolation and then washed out of nuclei before nuclease digestion. Using this procedure, 1mM p-chloromercuriphenyl sulfonate is as effective as 50mM bisulfite in retaining the phosphatase-sensitive mitotic phosphorylations of histones H1 and H3.

4-Chloromercuribenzenesulfonate↗

PubMed1983

Teratogenic effects of cholinergic insecticides in chick embryos--IV. The role of tryptophan in protecting against limb deformities.

The mechanism by which organophosphate (OP) insecticides cause micromelia in embryonic chick limbs was examined using a tissue culture approach. Limb bud cells in micromass culture were assayed for their proliferative and chondrogenic activities, [3H]thymidine and 35SO4 = incorporation, respectively, into the trichloroacetic acid-insoluble constituents of the cell masses and/or the accumulation of 35S-labeled soluble macromolecular products in the culture medium. There was no obvious correlation between either the teratogenicity or toxicity of the insecticide in ovo and the inhibition of proliferation and chondrogenesis in vitro. In addition, nicotinamide, which prevents insecticide-induced micromelia in ovo, did not improve the proliferative and chondrogenic performance of insecticide-treated cells in culture. On the other hand, 2-pyridinealdoxime methochloride, which offers little or no protection against micromelia in ovo, did protect both the proliferative and chondrogenic activities of the limb bud cells in micromass culture. These observations suggest that the actions of the insecticides on the cells in culture are not the same as those that produce micromelia in ovo. L-Tryptophan antagonized OP insecticide-induced micromelia in the embryo. In micromass culture, a much greater concentration of tryptophan was needed to support the chondrogenic than the proliferative activities of the limb bud cells. Moreover, a greater concentration of tryptophan was needed to support the chondrogenic activities of the leg bud than the wing bud cells. These in vitro responses of the limb bud cells to tryptophan deprivation are analogous to the in ovo response of the limbs to the teratogenic OP insecticides. A possible explanation of the roles of tryptophan and nicotinamide in preventing the limb deformities is offered.

Animals↗

PubMed1982

Evidence for more than one mechanism of action of the glucocorticoid hormones.

The data presented here provide evidence for at least two major cellular responses to the glucocorticoid hormones that do not seem to involve an interaction between the activated hormone-receptor complex and chromatin. We observed that 5mM pyridoxine in L-cell culture medium both increases the intracellular content of free pyridoxal phosphate by about 30% and decreases the glucocorticoid induction of glutamine synthetase to less than 30% of that at the normal (5 microM) concentration of the vitamin. Two other responses to the hormone-a major decrease in the polysome content of the cells and a decrease in the state of phosphorylation of ribosomal protein S6-are unaffected by the 5mM dose of the vitamin. In light of the findings of DiSorbo and Litwack ((1981) Biochem. Biophys. Res. Commun. 99, 1203-1208), pyridoxal phosphate appears to modulate the enzyme-inducing activity of dexamethasone in L-cells but not the polysome and ribosome related changes. These results are consistent with the hypothesis that certain important glucocorticoid induced responses are independent of nuclear function.

Animals↗

PubMed1982

Histone H2A phosphorylation in animal cells: functional considerations.

We have sought to determine the role of histone H2A phosphorylation in chromatin by examining the distribution of the phosphorylated and unphosphorylated forms of this core histone within the nuclei of mouse and human cells. At any time, only about 15% of the H2A of whole chromatin is in the phosphorylated form, and its phosphate is rapidly turned over, even in quiescent cells that contain a functional nucleus. The phosphorylations and dephosphorylations are not specifically relate to progress through the cell cycle, nor to DNA synthesis or repair, and they are not selectively nucleolar. Euchromatin is substantially enriched with phosphorylated H2A but is not the exclusive repository of it. Possible roles of this modification of H2A are considered.

Animals↗

PubMed1982

Do organophosphate insecticides inhibit the conversion of tryptophan to NAD+ in ovo?

The hypothesis that organophosphate (OP) insecticides reduce the NAD+ levels of chick embryos by inhibiting kynurenine formamidase was tested. Fertile chicken eggs at 3 days of incubation were treated with a teratogenic dose of the organophosphate insecticide diazinon (DZN) in the presence or absence of exogenous L-tryptophan or nicotinamide, or one of the metabolic intermediates (L-kynurenine, 3-hydroxyanthranilic acid, quinolinic acid) between tryptophan and NAD+. By day 10 of development, DZN reduced the NAD+ content of the hind limbs of the embryos to less than 20% of normal and by day 15 it caused severe type I and type II teratogenic responses. The co-presence of tryptophan or one of its metabolites served to maintain the NAD+ levels of DZN-treated embryos close to or above normal and significantly alleviated the symptoms of type I teratisms. Tryptophan is virtually as effective as most of its metabolites in suppressing the effects of DZN on the NAD+ content and physical development of the embryos. This equivalence does not support the proposition that the inhibition of kynurenine formamidase causes the lowered NAD+ levels involved in OP-induced type I teratogenesis. It is consistent with the concept that the insecticide acts to decrease the availability of tryptophan to the embryo.

Abnormalities, Drug-Induced↗

PubMed1981