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(327) Toxic Interactions of Metal/PAH Mixtures: Generations of reactive oxygen species leads to synergistic toxicity.
Greenberg, Bruce*,1, Huang, Xiao-Dong1, Babu, Sudhakar1, Tripuranthakan, Shree1, Lampi, Mark1, Diener, Lara1, Akhtar, Tariq1, Nykamp, Julie1, 1 Dept of Biology, University of Waterloo, Waterloo, ON, Canada
ABSTRACT- Interactions of Metal/PAH Mixtures: Reactive oxygen species leads to synergistic toxicity. Greenberg, BM, Huang, X-D, Babu, TS, Tripuranthakan, S, Lampi, M, El-Alawi, Y, Diener, L, Akhtar, T, Nykamp, J, University of Waterloo, Waterloo, ON N2L 3G1 Canada. Polycyclic aromatic hydrocarbons (PAHs) and heavy metals are two prevalent classes of contaminants in the environment. Because they often share the same production sources, they frequently co-exist in contaminated environments. However, few studies have focused on mixtures of metals and PAHs. Further, photooxidation of PAHs in the environment will generate many new species of compounds that have not been identified or thoroughly investigated. Therefore, the hazards of environmentally relevant mixtures of these two classes of chemicals have not been evaluated. Further, the biochemical mechanisms of the effects of these two classes of chemicals are virtually unknown. We have found that mixtures of metals and photomodified PAHs cause synergistic toxicity. The synergistic effects are induced by different modes of action of metals and photomodified PAHs. For instance, an anthracene photoproduct, 1,2 dihydroxyanthquinone, inhibits cytochrome b/f and cytochrome c reductase, and thus, interrupts electron transport in chloroplasts and mitochondria, respectively. The heavy metal Cu uses a catalytic mechanism to generate reactive oxygen species (ROS) by accepting electrons from overly reduced quinones, and succinate or NADH dehydrogenase. Thus, photomodified PAHs inhibit electron transport, while Cu harvests the electrons from the blocked bioenergitic membranes to generate high levels of ROS. This results in synergistic toxicity due to the high ROS loads. The effects of these types of mixtures on Lemna gibba, Daphnia magna and mammalian cell systems will be presented. This research has revealed an important catalytic mechanism of metal toxicity, that being apoptosis due to ROS formation. It also provides an explanation for observations of metal toxicity at very low concentrations.
Key words: Copper, Anthraquinone, Oxygen radicals, Mechanisms
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