Cellular effects induced by the antitumor agent azinomycin B.
Studies on the mechanism of action of the antitumor agent azinomycin B in vitro suggest that the drug elicits its lethal effects by the formation of interstrand crosslinks within the major groove of DNA. Here, we demonstrate the biological effects of the drug in vivo. Fluorescence imaging revealed localization of azinomycin B in the nuclear region of yeast. Moreover, experiments with oligonucleotide microarrays examined the effects of the drug across the yeast transcriptome. The results demonstrated a robust DNA damage response that supports the proposed role of the drug as a covalent DNA modifying agent. RT-PCR analysis validated the gene changes, and flow cytometry of azinomycin-treated yeast cells demonstrated a phenotypic S phase shift consistent with transcriptional effects.
Kelly
Gilbert T
GT
Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA.
Liu
Chaomin
C
Smith
Roger
R
Coleman
Robert S
RS
Watanabe
Coran M H
CM
D000478:Alkylation; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects; D004249:DNA Damage; D017931:DNA Primers; D004271:DNA, Fungal / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins; D009281:Naphthalenes / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D000970:Antineoplastic Agents; D017931:DNA Primers; D004271:DNA, Fungal; D036341:Intercellular Signaling Peptides and Proteins; D009281:Naphthalenes; D010455:Peptides; C051055:azinomycin B