Harold C Box

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This review surveys the work that has been done on free radical-induced DNA double lesions. Double lesions consist of two modifications of the DNA in close proximity. Double lesions can be generated by a single free radical-initiating event and the mechanism of formation often involves the participation of guanine. The identification of double lesions in(More)
Chemical-DNA adducts provide an integrated measure of exposure, absorption, bioactivation, detoxification, and DNA repair following exposure to a genotoxic agent. Benzo[a]pyrene (BaP), a prototypical polycyclic aromatic hydrocarbon (PAH), can be bioactivated by cytochrome P-450s (CYPs) and epoxide hydrolase to genotoxic metabolites which form covalent(More)
A new type of tandem base lesion has been observed in d(CpGpTpA) X-irradiated in aqueous solution. The lesion is attributed to the formation of a covalent bond between the C8 carbon atom of guanine and the methyl carbon atom of thymine. This tandem base lesion is formed in the absence of oxygen. It is the main product produced by ionizing radiation under(More)
The hydrolysis by nuclease P1 of the 16 common deoxydinucleoside monophosphates was examined. The rates of hydrolysis of phosphodiester bond differ by more than two orders of magnitude; dinucleotide monophosphates of the type d(TpN) being most resistant and d(GpN) being next most resistant. The profiles of a mixture of the 16 common dinucleoside(More)
The radiation chemistry of the oligomer d(TpApCpG) X-irradiated in aqueous solution containing glutathione was studied. Four products were isolated by HPLC and characterized by NMR spectroscopy. Two of the major products are isomers of a 5-hydroxy-5,6-dihydrothymine modification of d(TpApCpG). A dihydrothymine modification is also formed. The other major(More)
A single free radical-initiating event can produce a pair of base lesions in DNA oligomers exposed to ionizing radiation. Whereas double base lesions have been observed previously, the present study shows that double lesions may sometimes consist of a base lesion and an associated strand break. The mechanism for the formation of double lesions is discussed.(More)
Evidence for the involvement of oxidative stress in 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated tumor promotion has focused on non-initiated immune cells, tumor cell lines and non-initiated epidermis treated in vivo. This paper reports the effects of TPA on 8-hydroxydeoxyguanosine (8OHdG) formation and the generation of reactive oxygen species (ROS)(More)
Background:A long-standing hypothesis is that oxidative stress is a risk factor for cancer. Support for this hypothesis comes from observations of higher levels of oxidative damage in the DNA of WBC of cancer patients compared with healthy controls.Methods:Two generally overlooked types of DNA damage, the formamide modification and the thymine glycol(More)
Evidence is presented for the formation of products in irradiated dinucleoside monophosphates in which both bases are damaged. The dinucleoside monophosphates d(GpT), d(GpC), d(TpG) and d(CpG) were X-irradiated in oxygenated aqueous solution. Product identification was by NMR spectroscopy. In products containing double base lesions, guanine is converted to(More)
Free radicals interact with DNA bases to produce secondary radicals. The secondary radicals are reactive species and tend to interact with neighboring bases, resulting in DNA lesions with two adjacent modified bases. In this study the DNA oligomers d(CpApTpG) and d(CpGpTpA) were exposed to free radicals generated in anoxic aqueous solution by X irradiation.(More)