| Volume 5 (2000) pp 415-422 |
| Title |
THE PHYSICOCHEMICAL PROPERTIES OF SOME NEW AMINOPHOSPHONATES |
| Authors |
Halina Kleszczyńska, Janusz Sarapuk and Anna Dziamska |
| Abstract |
The hemolytic activity of some newly synthesized
aminomethanephosphonic acid derivatives was studied. The compounds studied
differed in their polarity and the hydrophobicity of the electronic substituents at
their nitrogen and carbon atoms. It was found that acyclic aminophosphonates
exhibited significantly stronger hemolytic properties than cyclic
aminophosphonates. To cause the same level of hemolysis of pig erythrocytes,
it was necessary to use about a tenfold higher concentration of cyclic
aminophosphonates than acyclic ones. The hemolytic activities of the
compounds were related to the possibilities of their incorporation into the lipid
phase of erythrocyte membranes. Once incorporated, they changed the fluidity
of those membranes; the changes were more pronounced in the case of cyclic
aminophosphonates. Acyclic compounds were also found to exhibit a slight
antioxidative activity, which may be a consequence of their stronger interaction
with the membrane lipids. The results obtained in the experiments performed
with the use of planar lipid membranes were similar to those obtained in the
hemolytic studies, i.e., acyclic aminophosphonates interacted more effectively
with those membranes. The general conclusion is that both stereochemistry and
hydrophobicity are the factors that determine the efficiency of the interaction of
the compounds studied with the model membranes used, and that most likely
location of aminophosphonates is the lipid phase of the erythrocyte membrane.
Another conclusion is that newly synthesized aminophosphonates may be used
as potentially good pesticides. |
| Address and Contact Information |
Department of Physics and Biophysics, Agricultural University, Wroclaw,
Norwida 25, 50-375, Poland |
 ![[Rozmiar: 1332 bajtĂłw]](pic/abstract.gif) |
| Volume 5 (2000) pp 423-431 |
| Title |
THE DETECTION AND CHARACTERIZATION OF RAT PROTEIN
RECOGNIZING DNA DAMAGED BY N-ACETOXYACETYLAMINOFLUORENE |
| Authors |
Monika Pietrowska1, Joanna Łanuszewska1, Zofia Walter2,
Joanna Rzeszowska-Wolny1 and Piotr Widłak1* |
| Abstract |
Proteins recognizing DNA damaged by the chemical carcinogen Nacetoxy-
acetylaminofluorene (AAAF) were analyzed in nuclear extracts from
rat tissues, using a 36 bp oligonucleotide as the substrate and an electrophoretic
mobility shift assay. Two major proteins that form complexes with DNA
damaged by AAAF were detected; one of them also bound DNA damaged by
cis-diammine-dichloroplatinum. The complex specific for AAAF-damaged
DNA contained protein loosely attached to nuclear components. It was
extracted with 0.1 M NaCl. The amount of this protein was estimated at about
105 copies per liver cell nucleus, and its probable size was about 42 kDa as
detected by the Southwestern blotting assay. Its affinity for DNA damaged by
AAAF was ~10-fold higher than that for undamaged DNA. Analogous AAAFDDB
(damaged-DNA-binding) proteins were also detected in extracts from rat
brain, testis and kidney tissue. The levels of such proteins were not affected in
rats treated with the carcinogen 2-acetylaminofluorene. |
| Address and Contact Information |
1Department of Experimental and Clinical Radiobiology, Center of Oncology, 44-100 Gliwice, Poland
2Department of Molecular Genetics, University of
Lodz, 90-237 Lodz, Poland.
* Corresponding author: phone: (48 32) 278 9672. fax: (48 32) 231 3512.e-mail: widlak@onkol.instonko.gliwice.pl |
|
| Volume 5 (2000) pp 433-440 |
| Title |
THE MACROMOLECULAR AGGREGATE AS A DRUG CARRIER |
| Authors |
Marek Langner1 and Maciej Ugorski*,2,3 |
| Abstract |
Traditionally, a drug is expected to be biologically active and at the
same time be able to ensure some sort of tissue or organ specificity. The latter
property is necessary to avoid undesirable side effects when toxic drugs are
being used. Such requirements are difficult to achieve only by changing the
chemical formula of the drug. For these reasons, within the last few years a new
pharmacological concept has been developed regarding delivery of biologically
active compounds by the use of macromolecular aggregates. The purposespecific
design of macromolecular aggregates, able to deliver drugs to a desired
location, is based on the assumption that different functions can be assigned to
the separate chemical entities forming the aggregate. With the help of such an
aggregate, the biologically active compound can be designed with solely its
pharmacological potency in mind and without considering any limitations
imposed by inaccurate delivery, such as undesired side effects. Specific
molecules of the aggregate would ensure desired compound distribution within
the organism. Furthermore, other molecules forming the aggregate should fulfill
additional functions, e.g. protecting the drug from degradation. Additionally,
aggregates formed from amphiphilic molecules should be capable of carrying
drugs that are difficult to use as therapeutic agents due to low solubility in
biological fluids (e.g. Taxol) or degradation (e.g. peptides, DNA). Such
aggregates can be constructed from natural or/and synthetic compounds. Taken
together, this creates possibilities of extending the spectrum of drug application
and allows for the introduction of new technological modifications. |
| Address and Contact Information |
1Institute of Physics, Wroclaw University of Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland,
2Faculty of Veterinary Medicine, Agricultural University, ul. Norwida 25, 50-375 Wroclaw, Poland,
3Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53-114
Wroclaw, Poland |
|
| Volume 5 (2000) pp 441-450 |
| Title |
DNA DAMAGE AND APOPTOSIS INDUCTION IN L1210
CELLS BY CIS-DIAMMINEDICHLOROPLATINUM(II)
AND ITS NEW AMINOFLAVONE ANALOGUE |
| Authors |
Ewa Ciesielska1, Kazimierz Studzian1, Elżbieta Zyner2,
Justyn Ochocki2 and Leszek Szmigiero1 |
| Abstract |
This work compares the biological properties of cis-diamminedichloroplatinum
(cisplatin) and its new analogue cis-[Pt(AF)2Cl2] (AF stands
for 3-aminoflavone), which contains two aminoflavone substituents as nonleaving
ligands. Both compounds were tested for their antiproliferative activity
against cultured L1210 cells, and their DNA interstrand crosslinking activity in
cells and in a cell-free system. Cisplatin was found to be an approximately 6
times more cytotoxic drug than its new analogue. Platinum complexes reacted
with purified calf thymus DNA in a cell-free system producing DNA interstrand
crosslinks. The kinetics of crosslink formation was very similar for both
compounds but the maximal level of crosslinks was 20% higher for cisplatin. In
cells, however, crosslinks were produced by cisplatin, whereas this type of
DNA lesion was almost undetected in cells treated with the aminoflavone
analogue as assayed by DNA alkaline elution. At higher drug concentrations,
strong degradation of DNA was observed in L1210 cells treated with cis-
[Pt(AF)2Cl2] but not in the cells incubated with cisplatin. This DNA degradation
seems to reflect very efficient apoptosis induction by cis-[Pt(AF)2Cl2] as the
electrophoretic patterns of DNA from cells incubated with this drug showed a
ladder typical for apoptotic cells. |
| Address and Contact Information |
1Department of General Chemistry, Medical University of Lodz,
2Department of Inorganic Chemistry, Medical University of Lodz, Poland |
|
| Volume 5 (2000) pp 451-467 |
| Title |
THE CHICKEN α- AND β-GLOBIN GENE DOMAINS AND THEIR CHROMATIN ORGANIZATION |
| Authors |
Félix Recillas-Targa |
| Abstract |
The eukaryotic genome is organized into discrete chromatin domains.
The globin groups of genes have been two of the classical biological systems to
study the relationship between gene regulation and chromatin structure during
development. The individual promoters, enhancers and silencers of the globin
genes are stage- and tissue-specific regulatory elements that are controlled by
the interaction of ubiquitous and erythroid nuclear factors. Such regulated
activation requires an optimal chromatin organization. Erythroid and
constitutive DNase I hypersensitive sites (DHs) contribute to chromatin domain
remodeling mediated by locus control region (LCR) activity and defined by
domain boundaries. A comparative analysis of the chicken α- and β-globin
domains will outline the relevance and effect of chromatin structure on gene
regulation. |
| Address and Contact Information |
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México,
Departamento de Genética Molecular, Apartado Postal 70-242
México D.F. 04510 |
|
| Volume 5 (2000) pp 469-481 |
| Title |
EVALUATION OF THE IMMUNOMODULATORY ACTIVITY OF
FOUR COMPOUNDS EXERTING ANTIMUTAGENIC EFFECTS ON
HUMAN LYMPHOCYTES IN VITRO |
| Authors |
Kazimierz Gąsiorowski*, Barbara Brokos
and Helena Tabaka |
| Abstract |
Four compounds previously described as antimutagenic for human
lymphocytes in vitro were tested on their immunomodulatory activity in
lymphocyte cultures. The standard immunocytochemical methods were applied
for microscopic examination of the percentual representation of the main
lymphocyte subpopulation. The results imply that all of the tested compounds
exhibited significant immunomodulatory effect, with that of fluphenazine being
the strongest, whereas that of todralazine is the weakest. Two of the tested
compounds: anthocyanins from Aronia melanocarpa fruit, and alkylresorcinols
from cereal grains, also exhibited a distinct immunomodulatory activity, and it
deserves adequate attention as an activity exerted by natural products,
commonly present in regular human diet.
The analysis of the proliferating cell fraction, and the estimation of the cell
proliferation rate suggest that the effect of the tested compounds might depend
on an increase in the number of lymphocytes which expressed their
differentiation antigens on the cell membranes. |
| Address and Contact Information |
Wroclaw Medical University, Department of Basic Medical Sciences,
14 Kochanowskiego Str., 51-601 Wroclaw, Poland.
*Corresponding author, fax:(+48 71) 3479211, e-mail: kaz@basmed.am.wroc.pl |
|
| Volume 5 (2000) pp 483-493 |
| Title |
EFFECT OF LIPOSOME COMPOSITION AND CHOLESTEROL ON
THE CELLULAR UPTAKE OF STAVUDINE BY HUMAN
MONOCYTE/MACROPHAGES |
| Authors |
Arun Katragadda, Roger Bridgman1 and Guru Betageri2 |
| Abstract |
The objective of this study was to determine the cellular uptake of
stavudine (an approved drug for AIDS treatment) by human
monocyte/macrophages (U 937). The effect of lipid used, cholesterol
concentration and the presence of charge on the liposome bilayer, on the
cellular uptake by monocyte/macrophages was investigated. Liposomes
employed in the study were prepared by reverse phase evaporation. The lipids
egg PC, DMPC, DPPC, DSPC, DMPG and sphingomyelin were employed in
this study. The effect of cholesterol on cellular uptake was studied by using
liposomes containing a constant amount of lipid and varying amounts of
cholesterol. Stearylamine or dicetylphosphate (10 mol%) was used to induce
positive or negative charge on the bilayer. The cells were separated from
liposomes by centrifugation in membrane filters and the amount of stavudine
taken up by macrophages was estimated using tritium labeled drug as a marker.
Stavudine uptake was found to be the maximum (approximately 950 ng/million
cells) in liposomes containing dipalmitoyl phosphatidylcholine (DPPC). The
presence of sphingomyelin, which increases bilayer rigidity decreased cellular
uptake of stavudine and the presence of negative charge on the bilayer,
enhanced the uptake of stavudine compared to positive charge. There is no
apparent difference in uptake when varying amounts of cholesterol was added
to liposomal formulations. The present study shows that the sensitivity of
macrophages to different charge and lipid type can be used to either decrease or
increase cellular uptake as desired. |
| Address and Contact Information |
Department of Pharmacal Sciences, School of Pharmacy, Auburn University,
Auburn, AL 36849 and 1Hybridoma Facility, A.U Research Park, Auburn
University, Auburn, AL 36849. 2Western University of Health Sciences,
College Plaza, 309 E. Second Street, Pomona, CA 91766. |
|
| Volume 5 (2000) pp 495-509 |
| Title |
IDENTIFICATION OF mRNA ENCODING HOMEOBOX PROTEINS
HOX b4 AND HOX b5 IN DEVELOPING CHICKEN GIZZARD
TISSUES |
| Authors |
Rebecca A. Fillmore and Warren E. Zimmer* |
| Abstract |
Combining reverse transcriptase-polymerase chain reaction (RTPCR)
and molecular cloning technologies, we have investigated the expression
of homeodomain proteins in chicken gizzard tissues undergoing differentiation.
We demonstrate that homeodomain encoding transcripts are found in
developing chicken gizzard. An RT-PCR generated 117 bp homeodomain
DNA probe was used to screen a gizzard library and resulted in the
identification of ~60 potential homeodomain encoding cDNAs. Sequence
analysis of the two longest clones identified them as Hox b4 and Hox b5,
paralogues of Drosophila Deformed (Dfd) and Sex combs reduced (Scr),
respectively. Northern blotting analysis demonstrated an increase in the Hox b4
and Hox b5 mRNAs just prior to the onset of smooth muscle cell differentiation
as judged by the expression of the smooth muscle g-actin gene. Thus, Hox b4
and Hox b5 display the appropriate temporal expression pattern to be involved
in the development/differentiation of the chicken gizzard. |
| Address and Contact Information |
Department of Cell Biology and Neuroscience,
University of South Alabama, College of Medicine,
Mobile, Alabama, 36688, USA
*Corresponding author |
|
