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Phospholipases A2 (PLA2) catalyze the hydrolysis of the ester bond at the sn-2 position of phospholipids to generate the lysophospholipid and free fatty acid (1). Several classes of PLA2s have been identified (2). They include the low molecular weight-secreted enzymes, which demonstrate a requirement for millimolar concentrations of Ca2+ for full activity and are generally involved in the inflammatory response. The high molecular-weight, cytosolic PLA2s are activated by submicromolar calcium, have specificity for unsaturated fatty acids and arachidonic acid in particular (3,4). The arachidonic acid released can have many direct functions or can serve as a precursor in the formation of the numerous prostaglandin and leukotriene products (5). Thus, it is becoming increasingly clear that this latter class of enzymes are the principle regulators of arachidonic-acid release and therefore play an important role in signal transduction (6). [ABSTRACT FROM AUTHOR]

Oxidative stress has been implicated in the etiology of many pathological states and known to result in DNA damage. Oxidative DNA damage can lead to mutagenesis (1-3) and has been associated with aging (4), diabetes mellitus (5), inflammatory disease (1) and carcinogenesis (1-3,6). The 8-hydroxy-2-deoxyguanosine lesion (8-OHdG) is often used in the assessment of oxidative DNA damage and has become the de facto marker for oxidative damage to DNA. 8-OHdG is one of the most prominent lesions observed following exposure to ionizing radiation (7) but also results from treatment with many xenobiotics (8) as well as by endogenous mechanisms. Thus, normal endogenous levels becomes a critical issue in the assessment of cellular 8-OHdG levels in pathological states. Furthermore, 8-OHdG is efficiently repaired by a DNA glycosylase specific for this lesion (9) and its contribution to mutagenesis is relatively weak (10-12). However, it is representative of approximately 20 additional oxidatively-denved lesions known to result from radiation damage (13) and whose mutagenic outcome are largely unknown in mammalian-cell systems. [ABSTRACT FROM AUTHOR]