Here, ten guidelines are presented for a standardized definition of type I and II photosensitized oxidation reactions. Because of varied notions of reactions mediated by photosensitizers, a checklist of recommendations is provided for their definitions. Type I and type II photoreactions are oxygen-dependent and involve unstable species such as the initial formation of radical cation or neutral radicals from the substrates and/or singlet oxygen (1O2 1Δg) by energy transfer to molecular oxygen. In addition, superoxide anion radical (O2•−) can be generated by a charge transfer reaction involving O2 or more likely indirectly as the result of O2-mediated oxidation of the radical anion of type I photosensitizers. In subsequent reactions, O2•− may add and/or reduce a few highly oxidizing radicals that arise from the deprotonation of the radical cations of key biological targets. O2•− can also undergo dismutation into H2O2, the precursor of the highly reactive hydroxyl radical (•OH) that may induce delayed oxidation reactions in cells. In the second part several examples of type I and type II photosensitized oxidation reactions are provided to illustrate the complexity and the diversity of the degradation pathways of mostly relevant biomolecules upon one-electron oxidation and singlet oxygen reactions.

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In this review article, emphasis is placed on the critical survey of available data concerning modified nucleobase and 2-deoxyribose products that have been identified in cellular DNA following exposure to a wide variety of oxidizing species and agents including, hydroxyl radical, one-electron oxidants, singlet oxygen, hypochlorous acid and ten-eleven translocation enzymes. In addition, information is provided about the generation of secondary oxidation products of 8-oxo-7,8-dihydroguanine and nucleobase addition products with reactive aldehydes arising from the decomposition of lipid peroxides. It is worth noting that the different classes of oxidatively generated DNA damage that consist of single lesions, intra- and interstrand cross-links were unambiguously assigned and quantitatively detected on the basis of accurate measurements involving in most cases high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry. The reported data clearly show that the frequency of DNA lesions generated upon severe oxidizing conditions, including exposure to ionizing radiation is low, at best a few modifications per 106 normal bases. Application of accurate analytical measurement methods has also allowed the determination of repair kinetics of several well-defined lesions in cellular DNA that however concerns so far only a restricted number of cases.

Although the general mechanisms of lipid oxidation are known, the chemical steps through which photosensitizers and light permeabilize lipid membranes are still poorly understood. Herein we characterized the products of lipid photooxidation and their effects on lipid bilayers, also giving insight into their formation pathways. Our experimental system was designed to allow two phenothiazinium-based photosensitizers (methylene blue, MB, and DO15) to deliver the same amount of singlet oxygen molecules per second to 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine liposome membranes, but with a substantial difference in terms of the extent of direct physical contact with lipid double bonds; that is, DO15 has a 27-times higher colocalization with ω-9 lipid double bonds than MB. Under this condition, DO15 permeabilizes membranes at least 1 order of magnitude more efficiently than MB, a result that was also valid for liposomes made of polyunsaturated lipids. Quantification of reaction products uncovered a mixture of phospholipid hydroperoxides, alcohols, ketones, and aldehydes. Although both photosensitizers allowed the formation of hydroperoxides, the oxidized products that require direct reactions between photosensitizer and lipids were more prevalent in liposomes oxidized by DO15. Membrane permeabilization was always connected with the presence of lipid aldehydes, which cause a substantial decrease in the Gibbs free energy barrier for water permeation. Processes depending on direct contact between photosensitizers and lipids were revealed to be essential for the progress of lipid oxidation and consequently for aldehyde formation, providing a molecular-level explanation of why membrane binding correlates so well with the cell-killing efficiency of photosensitizers.

Singlet molecular oxygen (1O2) has been shown to be generated in biological systems and is capable of damaging proteins, lipids and DNA. The ability of some biological antioxidants to quench 1O2 was studied by using singlet oxygen generated by the thermodissociation of the endoperoxide of 3,3'-(1,4-naphthylidene) dipropionate (NDPO2). The carotenoid lycopene was the most efficient 1O2 quencher (kq + kr = 31 x 10(9) M-1 s-1). Tocopherols and thiols were less effective. The singlet oxygen quenching ability decreased in the following order: lycopene, gamma-carotene, astaxanthin, canthaxanthin, alpha-carotene, beta-carotene, bixin, zeaxanthin, lutein, bilirubin, biliverdin, tocopherols and thiols. However, the compounds with low quenching rate constants occur at higher levels in biological tissues. Thus, carotenoids and tocopherols may contribute almost equally to the protection of tissues against the deleterious effects of 1O2. The quenching abilities of carotenoids and tocopherols were mainly due to physical quenching. In case of some thiols chemical quenching also plays a significant role. Carotenoids and tocopherols have been reported to exert a protective action against some types of cancer.