The early history of polyamine research.

In 1678 Antonie van Leeuwenhoek identified crystalline substances in human semen. The structure of these crystals, named "spermine", was not elucidated by Rosenheim until 250 years later. Subsequently a triamine (spermidine) and a diamine (putrescine; 1,4-diaminobutane) were isolated from prokaryotic and eukaryotic systems.

Antiviral activity of oxidized polyamines.

Polyamines, oxidized by serum amine oxidase, yield aminoaldehydes and hydrogen peroxide. Acrolein may be formed from the aminoaldehydes by a spontaneous beta-elimination process. These oxidation products "oxidized polyamines" inhibit bacterial growth and exhibit anticancer activity.

Naturally occurring polyamines: interaction with macromolecules.

The naturally occurring polyamines, spermine [NH2(CH2)3NH(CH2)4NH(CH2)3NH2] and spermidine [NH2(CH2)3NH(CH2)4NH2], as well as the diamine putrescine [NH2(CH2)4NH2], are widely spread in nature. They occur in plants, micro-organisms and animal tissues and fulfil many important physiological functions. Due to their cationic nature they interact with negatively charged macromolecules such nucleic acids, phospholipids and proteins.

Immunohistochemical detection of ornithine decarboxylase as a measure of chemosensitivity testing.

The development of reliable methods for the in vitro testing of sensitivity of cancer cells to various drugs has been a longstanding objective in cancer treatment. The development of individualized chemotherapy could minimize undesired toxic side effects and increase the chance of recovery. The known methods for in vitro chemosensitivity tests are mainly based on monitoring the metabolic changes induced in cancer cells by the drugs.

Polyamines and cancer: minireview article.

The naturally occurring polyamines, spermine, spermidine and the diamine putrescine are widespread in nature. They have been implicated in growth and differentiation processes. Polyamines accumulate in cancerous tissues and their concentration is elevated in body fluids of cancer patients.

The opposing effects of endothelin-1 and C-type natriuretic peptide on apoptosis of neonatal rat cardiac myocytes.

C-type natriuretic peptide (CNP) and endothelin-1 are paracrine peptides with opposing effects on cardiac myocyte contraction and intracellular cGMP production. Elevated levels of both endothelin-1 and CNP are found in patients with congestive heart failure. These factors may be related to positive and negative regulation of cell apoptosis in the failing heart.

In vitro chemosensitivity testing of hematological cancer patients: detection of ornithine decarboxylase.

The development of reliable methods for the in vitro testing of sensitivity of cancer cells to various drugs has been a longstanding objective in cancer research and treatment Early attempts to develop individualized chemotherapy were based on clonogenic assays. These attempts failed because of low plating efficiencies. Nonclonogenic assays, such as the MMT test or ATP determinations, are based on metabolic activities and do not reflect the ability of cells to proliferate.

The specific anti-cancer activity of green tea (-)-epigallocatechin-3-gallate (EGCG).

The effect of the green tea polyphenol-(-)epigallocatechin-3-gallate (EGCG) was tested in cultures of normal and transformed NIH-pATM ras fibroblasts. In this system transformation can be induced at will by the addition of dexamethasone, which induces the expression of H- ras by activating the mammary tumor virus long terminal repeat (MMTV-LTR) promoter. This facilitates a reliable comparison of the susceptibility of normal and transformed cells to EGCG.

Cancer therapy and prevention by green tea: role of ornithine decarboxylase.

Green tea which is widely consumed in China, Japan and India, contains polyphenolic compounds, which account for 30% of the dry weight of the leaves. Most of the polyphenols are flavanols, of which (-)-epigallocatechin-3-gallate (EGCG) is most abundant. Epidemiological studies revealed that the incidences of stomach and prostate cancers are the lowest in the world among a population that consumes green tea on a regular basis.

Polyamines: new cues in cellular signal transduction.

The naturally occurring polyamines putrescine, spermidine, and spermine are involved in signal transduction. This has been demonstrated by using inhibitors for polyamine biosynthesis (such as alpha-difluoromethylornithine) or adding polyamines to cultured cells. Different polyamines, preferentially activated protein kinases (tyrosine kinases and MAP kinases), stimulated the expression of nuclear protooncogenes (myc, jun, and fos).

A luminescence-based test for determining ornithine decarboxylase activity.

A sensitive chemiluminescence-based method for the assay of ornithine decarboxylase (ODC) has been developed. This method, which permits the detection of putrescine (the product of ODC) at a picomolar range, can be used to determine ODC activity in cellular extracts. Extracts are incubated with ornithine and spotted onto p81 phosphocellulose paper strips.

Effects of testosterone and 17, beta-estradiol on the polyamine metabolism in cultivated normal rat kidney epithelial cells.

Ornithine decarboxylase (ODC) and diamine oxidase (DAO) are important enzymes involved in the metabolism of polyamines (putrescine, spermidine and spermine). The influence of testosterone (T) and 17, beta-estradiol (E2) on the activity of ODC and DAO was examined in cultivated normal rat kidney (NRK) epithelial cells. The results showed an increase in enzyme activities 4 hours or 12 hours after hormonal treatment.

Role of polyamines in mediating malignant transformation and oncogene expression.

Previous studies have demonstrated that polyamines accumulate in cancer cells and that overproduction of ornithine decarboxylase (ODC), which catalyzes polyamine synthesis, elicits the acquisition of the transformed phenotype. However, it was not clear whether the expression of ODC and the accumulation of polyamines are only innocent by-products of the transformation process. In this study we confirm previous findings what polyamines can trigger the transformation of immortalized cultured cells.

In vitro chemosensitivity testing of hematological cancers: immunohistochemical detection of ornithine decarboxylase.

A new method for in vitro chemosensitivity testing of human lymphoma and leukemia patients has been developed. The method is based on the use of ornithine decarboxylase (ODC), a universal marker of proliferation, which is expressed early during the cell cycle and has a short half-life. This marker was detected by a quantitative immunohistochemical analysis, using an ODC antibody and a FITC-linked second antibody.

Developmental aspects of polyamine-oxidizing enzyme activities in the mouse kidney. Effects of testosterone.

In the present study developmental patterns of renal polyamine-oxidizing enzymes polyamine oxidase (PAO) and diamine oxidase (DAO) in male and female ICR mice were demonstrated. The effects of testosterone (10 micrograms/100g body weight) on renal PAO and DAO activities were also studied. The differences between sexes in both PAO and DAO activities were most clearly expressed in the immature kidney.

Polyamines induce malignant transformation in cultured NIH 3T3 fibroblasts.

Previous studies have demonstrated that polyamines accumulate in cancer cells and that overproduction of ornithine decarboxylase (ODC), which catalyzes polyamine synthesis, elicits the acquisition of the transformed phenotype. However, it was not clear whether the overexpression of ODC and the accumulation of polyamines are only innocent by-products of the transformation process. In this study we demonstrate that polyamines as such, may play a crucial role in malignant transformation.

Ornithine decarboxylase: an indicator for growth of NIH 3T3 fibroblasts and their c-Ha-ras transformants.

Growth rates of different clones, all derived from NIH 3T3 mouse fibroblasts, were determined. Four different types of cells were studied: (1) Normal NIH 3T3 fibroblasts; (2) a fast-growing NIH 3T3 clone obtained by repeated passages; (3) transformed clones (obtained by transfecting NIH 3T3 with the oncogene c-Ha-ras); (4) a slow-growing revertant obtained by repeated passages of the transformed line. Growth rates were determined by the following markers of proliferation: thymidine incorporation, protein accumulation and cell number.

Ornithine decarboxylase--a predictor for tumor chemosensitivity.

The activity of ornithine decarboxylase (ODC) was determined in P388 murine leukemia cells treated with adriamycin (ADR) and methotrexate (MTX). Some of the cell lines were resistant to ADR, MTX or their combinations. A similar pattern was found between the cytotoxicity and the suppression of ODC activity in these cell lines in terms of drug concentrations.

Activation of the proto-oncogene c-myc and c-fos by c-ras: involvement of polyamines.

Rat kidney cells infected with a temperature-sensitive mutant of Kirsten sarcoma virus (Ki-MSV ts 371) expressed Ki-Ras at 37 degrees C but not at 42 degrees C. This expression of the oncogene was accompanied by an increase in the activity of ornithine decarboxylase (ODC) and the accumulation of putrescine. Elevation of cellular polyamine content triggered the transcription of c-myc and c-fos.

Immunohistochemical detection of ornithine decarboxylase in individual cells: potential application for in vitro chemosensitivity assays.

Ornithine decarboxylase (ODC), which catalyzes the rate-limiting step in the biosynthesis of polyamines, can serve as a marker of proliferation. The presence of ODC protein in individual cells was quantitatively detected by an immunofluorescence assay using an ACAS 570 computerized fluorescence microscope. ODC was detected in KB-3-1 human epithelial carcinoma cells grown in the absence of any drug.

Determination of multidrug resistance levels in cultured mammalian cells using ornithine decarboxylase activity.

We describe an ornithine decarboxylase (ODC) activity-based assay for the quantitation of multidrug resistance (MDR) and its reversal by MDR modulators in cultured mammalian cells. ODC catalyzes the first and rate-limiting step in polyamine biosynthesis. The activity of this enzyme rises rapidly after growth initiation, such as after addition of serum-containing medium to quiescent mammalian cells.

Changes in brain polyamine levels following head injury.

The changes in polyamines levels in the brain after closed head injury were studied in rats. At 1 and 15 min, 24 and 48 h after closed head injury cortical tissue from the site of injury, from the contralateral region, and from remote areas were taken. The levels of the diamine putrescine and the polyamines spermine and spermidine were assayed by thin layer liquid chromatography of their dansyl derivatives.

Effect of sinefungin on macromolecular biosynthesis and cell cycle of Plasmodium falciparum.

The growth of the malarial parasite P. falciparum was arrested by the adenine containing nucleoside sinefungin at the trophozoite stage. The synthesis of DNA, of polyamines and the specific proteins of the schizont stage were completely blocked by the drug.