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Binding and alkylation of DNA
Interference with DNA unwinding and separation process through the
inhibition of the enzyme helicase
The inhibition of Toposisomerase II
o Increase in apoptosis
Although the number of mechanisms are thought to be involved in the adriamycin's
antineoplastic effects, recent studies indicate that the combination of the inhibition of
topoisomerase II function, p53-induced apoptosis and direct damage to DNA may be the
most prominent features of adriamycin's antitumor activity.
I.c. Toxic effects of Adriamvcin
Adriamycin administration is associated with significant number of general toxic
effects, all of them are found to be manageable and clinically reversible. However, the
major clinical problem of adriamycin administration is its potential for the induction of
irreversible myocardial damage. This damage can lead to the development of druginduced
cardiomyopathy. Based on the times of their onset, all cardiotoxic effects of
adriamycin can be divided into three groups: acute, subacute and chronic.
I.c.l. Acute cardiotoxicity: Acute cardiotoxicity is characteized by the early onset,
minutes or hours after the intravenous administration of adriamycin. These include
sudden developrnent of hypotension, tachycardia and arrhythmias (Ferrans lg78).
Adriamycin-induced acute hypotension is thought to be caused by an increase in the
plasma levels of circulating histamines (Bristow et al. 1981; Herman et al. 1978). This
hypothesis is supported by the fact that adriamycin-induced hypotension can be
prevented by the pre-administration of histamine-release and histamine-receptor blocking