Effects of spermine on formation of HGPRT⁻ mutants induced by ethylmethanesulfonate, methylmethanesulfonate, and mitomycin C in V79 chinese hamster cells

Abstract

Spermine is a polyamine found in bacteria, animal, and plant tissues. It is involved in a variety of biological processes, and its interaction with DNA stabilizes the secondary structure of the double helix. Spermine is one of the first reported antimutagens, reducing the mutation rate in several prokaryotic test systems, while in eukaryotic organisms conflicting results have been obtained. In light of the significant antimutagenic effect of spermine, it is important to evaluate its activity in mammalian cells in culture. The present study was undertaken to evaluate the ability of spermine to suppress the level of HGPRT- mutants induced by ethylmethanesulfonate, methylmethanesulfonate, and mitomycin C. Spermine reduced the mutation frequency induced by ethylmethanesulfonate and methylmethanesulfonate but did not affect survival; with mitomycin C survival was reduced but mutation rate was not influenced.

Amifostine—Antioxidant Drug in Anticancer Therapy

“…Particularly, the 1,3-diaminopropanic part of amifostine molecule as well as WR-1065 and WR-33278 compounds are similar to spermine and spermidine (Table 2) (Grdina et al 2000). Polyamine degradation is catalyzed by amino oxidases, enzymes that are characterized by wide action range (Fiorio et al 1994;Mondovi et al 1988). Taking into consideration both the foregoing data as well as the hitherto existing experimental results, WR-1065 is supposed to be a substrate for amino oxidases, dependent on copper ions, as a result of which very reactive compounds, including acrolein, cystamine, and hydrogen peroxide, are generated ( Fig.…”

“…Nevertheless, the disulfide form WR-1065 may inhibit activity of specific DNA endonucleases (Grdina et al 2000). Moreover, it may be assumed that the disulfide form, due to its structure and properties similar to polyamines, may also stabilize chromatine and affect the DNA synthesis, kinase activity, gene expression, and protein structure (Fiorio et al 1994). It has been found that aminothiols can bind and stabilize this part of the DNA helix, which is not protected by histones (Brown 1967), and amifostine metabolites compete against polyamines for binding sites in DNA .…”

Φωτοδυναμική Θεραπεία Στην Κάθαρση Νεοπλασματικών Κυττάρων Από Το Μυελό Και Το Περιφερικό Αίμα Παιδιών Με Κακοήθειες

“…Ο γρήγορος ρυθµός κάθαρσης από το πλάσµα οφείλεται στην περιφερική ενεργοποίηση και πρόσληψη του WR-1065 από τους ιστούς.Το συµµετρικό δισουλφίδιο WR-33278 παρουσιάζει δοµική οµοιότητα µε την πολυαµίνη, σπερµίνη[340]. Οι πολυαµίνες είναι πολυκατιονικά µόρια που βρίσκονται σε όλα τα κύτταρα και συµµετέχουν σε ενδοκυτταρικές διαδικασίες που επηρεάζουν τη σταθεροποίηση της χρωµατίνης, τη σύνθεση DNA, τη δραστηριότητα κινασών, την έκφραση γονιδίων και τη διαµόρφωση των πρωτεϊνών[341]. Το WR-33278 ανταγωνίζεται για τις ίδιες θέσεις σύνδεσης µε τις πολυαµίνες στο DNA και αναστέλλει τη σύνθεσή του επιτρέποντας στο κύτταρο να επιδιορθώσει τα κατεστραµένα από την χηµειοθεραπεία ή ακτινοθεραπεία τµήµατα DNA.…”