Unraveling the causes
underlying polycyclic aromatic hydrocarbon
phototoxicity is an essential step in understanding the harmful effects
of these compounds in nature. Toward this end, we have studied the
DNA interactions and photochemistry of N
1-(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride in the presence
and absence of NaF, KF, NaCl, KCl, NaBr, KBr, NaI, and KI (350 nm
hν, pH 7.0). Exposing pUC19 plasmid to UV light in solutions
containing 400 mM KCl formed significantly more direct strand breaks
in DNA compared to no-salt control reactions. In contrast, NaCl increased
DNA damage moderately, while the sodium(I) and potassium(I) fluoride,
bromide, and iodide salts generally inhibited cleavage (I– > Br– > F–). A halide
anion-induced
heavy-atom effect was indicated by monitoring anthracene photodegradation
and by employing the hydroxyl radical (•OH) probe
hydroxyphenyl fluorescein (HPF). These studies revealed that among
no-salt controls and the eight halide salts, only NaCl and KCl enabled
the anthracene to photosensitize the production of high levels of
DNA-damaging reactive oxygen species (ROS). Pre-irradiation of N
1-(anthracen-9-ylmethyl)ethane-1,2-diaminium
dichloride at 350 nm increased the amounts of chloride salt-induced •OH detected by HPF in subsequent anthracene photoactivation
experiments. Taking into consideration that •OH
and other highly reactive ROS are extremely short-lived, this result
suggests that the pre-irradiation step might lead to the formation
of oxidized anthracene photoproducts that are exceedingly redox-active.
The fluorometric probes HPF and Singlet Oxygen Sensor Green revealed
that KCl concentrations ranging from 150 to 400 mM and from 100 to
400 mM, respectively, enhanced N
1-(anthracen-9-ylmethyl)ethane-1,2-diaminium
dichloride photosensitized •OH and singlet oxygen
(1O2) production over no-salt controls. Considering
the relatively high levels of Na+, K+, and Cl– ions that exist in the environment and in living organisms,
our findings may be relevant to the phototoxic effects exhibited by
anthracenes and other polycyclic hydrocarbons in vivo.