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J Med Oncl Ther 2017 | Volume 2 Issue 3

Breast Cancer

November 01-02, 2017 | Toronto, Canada

World Congress on

or more than 40 years, anthracyclines have represented

one of the most commonly used anticancer drugs.

Doxorubicin and epirubicin are the morst common chemicals

used against breast cancer, It is known that anthracyclines

interact with the DNA double helix in a variety of very

complex manners, which include intercalation of doxorubicin

into the DNA duplex, formation of formaldehyde-mediated

DNA crosslinks (primarily between neighboring guanines),

and the catalytic inhibition of DNA topoisomerse II.

Numerous studies in our lab have shown that four

anthracyclines (daunorubicin, idarubicin, doxorubicin,

and epirubicin) can induce DNA base excision repair and

O6 alkylguanine DNA repair alkyltransferase- dependent

base-substitution events and frameshift mutaions in the

bacterium Salmonella typhimurium. More recent studies

evaluated the recombinogenic potential of anthracyclines in

a eukaryotic unicellular organism Saccharomyces cerevisiae.

In the yeast deletion (DEL) assay, recombination is induced

by the formation of DNA strand breaks, which are a substrate

for initiation of genetic repair in this organism. Using the DEL

assay, our lab has examined the role of DNA recombination

pathways in the recognition and removal of anthracycline-

induced DNA adducts. Specifically, doxorubicin (49.1 fold)

and epirubicin (279 fold) tested positive in this assay. Our

next step is to examine the pre-carcinogenic anthracycline-

dependent events in mammals.

Mutagenic and Cytotoxic Effects of Doxorubicin (Adriamycin) and Epeirubicin, Common Anthracycline

DNA II Topoisomerase Inhibitors Used Against Breast Cancer, in Prokaryotic and Eukaryotic Cells

William J Mackay

Edinboro University, USA