Carcinogenic semicarbazide induces sequence-specific DNA damage through the generation of reactive oxygen species and the derived organic radicals.
ABSTRACT Semicarbazide, a hydrazine derivative, is carcinogenic to mice but shows no or little mutagenicity in the Salmonella-microsome test. To clarify whether or not the genotoxic mechanism contributes to the non-mutagenic carcinogenicity of semicarbazide, we investigated DNA damage induced by semicarbazide using 32P-5'-end-labeled DNA fragments obtained from the c-Ha-ras-1 protooncogene and the p53 tumor suppressor gene. Semicarbazide caused DNA damage frequently at the thymine and cytosine residues in the presence of Cu(II). Catalase and bathocuproine partially inhibited DNA damage, suggesting that hydrogen peroxide plus Cu(I) participates in DNA damage. When a high concentration of semicarbazide was used in the presence of catalase, DNA damage was induced, especially at G in 5'-AG and slightly at 5'-G in GG and GGG sequences. An electron paramagnetic resonance (EPR) spectroscopic study has confirmed that the reaction of semicarbazide with Cu(II) produces carbamoyl radicals (z.rad;CONH(2)), possibly generated via the nitrogen-centered radicals of semicarbazide. Azodicarbonamide also produced carbamoyl radicals and induced DNA damage frequently at 5'-G in GG and GGG sequences, suggesting that carbamoyl radicals participate in this sequence-specific DNA damage by semicarbazide. On the basis of our previous reports, we consider that the sequence-specific DNA damage at G in 5'-AG in the present study is due to the nitrogen-centered radicals. This study has shown that semicarbazide induces DNA damage in the presence of Cu(II) through the formation of hydrogen peroxide and Cu(I). In addition, semicarbazide-derived free radicals participate in DNA damage. DNA damage induced by these reactive species may be relevant to the carcinogenicity of semicarbazide.
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ABSTRACT: Currently, a number of food producers use hypochlorite to bleach food and inhibit the growth of bacteria, preserving the food. Because the presence of high amounts of nitrogen could result in the formation of semicarbazide (SEM), the bleaching process could be one of the predominant sources of SEM in food. To investigate this, we selected instant bottled bird's nest as an example of a food that is bleached in its production. SEM was detected in 27 of 28 instant bottled bird's nest samples. The levels of SEM detected mostly fell in the range of 5 to 50 μg/kg, which accounted for 75% of all samples measured. The SEM detected in the instant bottled bird's nest was found to have originated neither from the use of the antimicrobial agent nitrofurazone nor from azodicarbonamide, which is used as a blowing agent in gaskets used to seal the metal lid of the bottle. Instead, it could have originated from the bleaching process used in the preparation of the nests. Additionally, human exposure to SEM via consumption of instant bottled bird's nest for five subgroups of the population was estimated. Sensitivity analysis suggested that concentration of SEM in food is the most significant parameter governing human exposure via consumption of SEM-containing food.Journal of food protection 09/2012; 75(9):1654-9. · 1.83 Impact Factor
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ABSTRACT: Mining effluents are the main source of metals in the surrounding aquatic environment. The mining district of Purple Mountain has a history of copper mining for more than 30 years, but there is limited investigation of metal bioaccumulation in the aquatic creatures from the Tingjiang river catchment affected by the mining activities. In this study, we collected grass carps (Ctenopharyngodon idellus) from four sites, and analyzed the accumulation of chromium (Cr), nickel (Ni), manganese (Mn), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in ten tissues (scale, skin, muscle, gill, liver, kidney, fish maw, heart, stomach, and intestine) of the fish samples. Among all tissue samples, the highest concentrations (micrograms per gram wet weight) of Ni (0.263), Cu (69.2), Zn (84.0), As (0.259), Cd (0.640), Hg (0.051), and Pb (0.534) were noted in the liver, gill, and kidney tissues, whereas the highest concentrations of Cr (0.356) and Mn (62.7) were detected in the skin and intestine, respectively. These results gave a better understanding of the variability of metals distribution in different fish tissues. In comparison with the sample sites, metals (especially Mn, Cu, Zn, Ni, and Pb) in liver, gill, kidney, stomach, and intestine showed more inter-site differences than other tissues. The inter-site differences also revealed that site 1 and 2 increased fish uptake of Cu, Zn, Ni, and Pb, which may indicate that the copper mine and urban effluents contributed to high levels of these metals in aquatic environments in site 1 and 2. A potential food safety issue may emerge depending on the mining activities in this region because some metals in a few tissue samples exceeded the guideline values for human consumption of fish.Environmental Monitoring and Assessment 07/2011; 184(7):4289-99. · 1.68 Impact Factor
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ABSTRACT: A direct ELISA was established for the fast detection of semicarbazide (SEM) using a novel biotin derivative. Without a tedious extraction procedure, as low as 0.07 μg L(-1) of SEM could be detected reproducibly. This assay has better recovery and accuracy than competitive ELISA.Chemical Communications 06/2013; · 6.38 Impact Factor