Pyrex-filtered UV light irradiation of d(BrCG) and 5-bromocytosine-containing duplex DNA leads to facile formation of a cross-link lesion between the C5 carbon atom of cytosine and the C8 carbon atom of its adjacent guanine. A similar cross-link lesion has been previously found in the X-ray irradiation mixture of d(CGTA).

The replacement of thymidine with 5-bromo-2′-deoxyuridine (BrdU) is well-known to sensitize cells to ionizing radiation and photoirradiation. We reported here the sequence-dependent formation of intrastrand crosslink products from the UVB irradiation of duplex oligodeoxynucleotides harboring a BrdU or its closely related 5-bromo-2′-deoxycytidine (BrdC). Our results showed that two types of crosslink products could be induced from d(BrCG), d(BrUG), d(GBrU), or d(ABrU); the C(5) of cytosine or uracil could be covalently bonded to the N(2) or C(8) of its neighboring guanine, and the C(5) of uracil could couple with the C(2) or C(8) of its neighboring adenine. By using those crosslink product-bearing dinucleoside monophosphates as standards, we demonstrated, by using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), that all the crosslink products described above except d(G[N(2)-5]U) and d(G[N(2)-5]C) could form in duplex DNA. In addition, LC-MS/MS quantification results revealed that both the nature of the halogenated pyrimidine base and its 5′ flanking nucleoside affected markedly the generation of intrastrand crosslink products. The yields of crosslink products were much higher while the 5′ neighboring nucleoside was a dG than while it was a dA, and BrdC induced the formation of crosslink products much more efficiently than BrdU. The formation of intrastrand crosslink products from these halopyrimidines in duplex DNA may account for the photosensitizing effects of these nucleosides.

The neural system is a multifunctional perceptual learning system. Our brain can perceive different kinds of information to form senses, including touch, sight, hearing, and so on. Mimicking such perceptual learning systems is critical for neuromorphic platform applications. Here, an artificial tactile perceptual neuron is realized by utilizing electronic skins (E-skin) with oxide neuromorphic transistors, and this artificial tactile perceptual neuron successfully simulates biological tactile afferent nerves. First, the E-skin device is constructed using microstructured polydimethylsiloxane membranes coated with Ag/indium tin oxide (ITO) layers, exhibiting good sensitivities of ∼2.1 kPa–1 and fast response time of tens of milliseconds. Then, the chitosan-based electrolyte-gated ITO neuromorphic transistor is fabricated and exhibits high performance and synaptic responses. Finally, the integrated artificial tactile perceptual neuron demonstrates pressure excitatory postsynaptic current and paired-pulse facilitation. The artificial tactile perceptual neuron is featured with low energy consumption as low as ∼0.7 nJ. Moreover, it can mimic acute and chronic pain and nociceptive characteristics of allodynia and hyperalgesia in biological nociceptors. Interestingly, the artificial tactile perceptual neuron can employ “Morse code” pressure-interpreting scheme. This simple and low-cost approach has excellent potential for applications including but not limited to intelligent humanoid robots and replacement neuroprosthetics.

Nucleoside 5-bromo-2'-deoxyuridine (BrdU), after being incorporated into cellular DNA, is well-known to sensitize cells to ionizing radiation and UV irradiation. We reported here, for the first time, the sequence-dependent formation of intrastrand cross-link products from the UVB irradiation of BrdU-treated MCF-7 human breast cancer cells. Our results showed that BrdU replaced more than 30% dT in genomic DNA after the cells were treated with 10 microM BrdU for 48 h. LC-MS/MS data revealed that more than 50% of the incorporated BrdU was consumed during UVB irradiation, of which more than half was dehalogenated to yield dU. Low-dose (5.0 kJ/m2) UVB irradiation of BrdU-treated cells yielded four intrastrand cross-link products, where the C5 of uracil is covalently bonded to the C8 of its neighboring 5' or 3' guanine to give G[8-5]U and U[5-8]G, respectively, and the C5 of uracil could couple with the C2 or C8 of its vicinal 5' adenine to give A[2-5]U and A[8-5]U, respectively. All the above cross-link products except A[2-5]U could also be induced in BrdU-treated cells upon UVB irradiation at a dose of 39 kJ/m2. We further demonstrated, by using LC-MS/MS, that the yield of G[8-5]U was much greater than the total yields of A[2-5]U and A[8-5]U. In addition, our results revealed that BrdU treatment stimulated considerably the UVB-induced formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in vivo. The formation of these intrastrand cross-link products and 8-oxo-dG in vivo underscores the importance of these products in the photosensitizing effect of BrdU.

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