Modulation of the genotoxicity of bleomycin by amines through noncovalent DNA interactions and alteration of physiological conditions in yeast

Synthesis, characterization and biological activities of mononuclear Co(III) complexes as potential bioreductively activated prodrugs

“…About the antibiotics activated prodrugs, bleomycin (a glycopeptide antibiotic) is probably the most studied by now, and is also a DNA cleaving agent, inducing double strand break by the involvement of iron and reduced oxygen species [15]. Recently, it was shown that amines can affect the genotoxicity of bleomycin in Saccharomyces cerevisiae through non covalent interactions [16], and that cell wall and plasma membrane act as independent barriers for bleomycin [17]. In addition, the presence of a membrane protein responsible for bleomycin internalization and toxicity in S. cerevisiae was reported [17].…”

Emerging approaches in predictive toxicology

“…A largely overlooked aspect of chemical entity/DNA binding is that which occurs in a noncovalent fashion, for example, by hydrogen bonding‐associated intercalation or groove binding. Noncovalent binding has been the subject of a recent Special issue of mutation research [Snyder, ] within which the chemistry [Strekowski and Wilson, ] and the biology [Ferguson and Denny, ; Hoffmann et al, ; Nelson et al, ] of such interactions are discussed. In addition, the evidence in favor of a directed evolutionary process driving small molecule intercalation in a regulatory role [Hendry et al, ] and the involvement of topoisomerases in the genotoxicity of intercalating agents is presented.…”

A Perspective on the Scientific, Philosophical, and Policy Dimensions of Hormesis

“…Toxicologists have long recognized that biological effects need not be additive, and interactions among agents can take diverse forms. One agent may potentiate another or, if both are themselves active, their combined effects can be synergistic (Hoffmann et al 2007). Alternatively, the interactions can be antagonistic, such that one agent diminishes the effects of another.…”

“…The latter includes antimutagenic and anticarcinogenic effects (Hartman and Shankel 1990; De Flora and Ferguson 2005). Such interactions are of interest for their potential application in the prevention of cancer or other disorders (De Flora and Ferguson 2005), but caution is required because the same agent that is protective under one set of conditions may be mutagenic, carcinogenic, or enhance the adverse activity of other agents under other conditions (Zeiger 2003; Hoffmann et al 2007).…”