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Abstract: This study investigated nucleic acid oxidation associated with styrene exposure, mRNA expression levels of hOGG1 gene and the role of the genetic polymorphism Ser326Cys of human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) in 60 styrene-exposed workers and 50 unexposed clerks. Biomarkers of exposure (styrene in blood, mandelic and phenylglyoxylic acids and 4-vinylphenol in urine) and urinary biomarkers of nucleic acid oxidation, namely 8-oxo-7,8-dihydro-2′-deoxyguanosine (U-8-oxodGuo), 8-oxo-7,8-dihydroguanosine (U-8-oxoGuo) and 8-oxo-7,8-dihydroguanine (U-8-oxoGua) were determined by liquid chromatography–tandem mass spectrometry. The levels of 8-oxodGuo adduct and 2′-deoxyguanosine (dGuo) were measured by HPLC in DNA from white blood cells (WBC). Genomic DNA and RNA from blood samples were used to characterize the Ser326Cys polymorphism and the mRNA expression levels of the hOGG1 gene, respectively, by PCR-based methods. Exposed workers showed lower values of 8-oxodGuo/105 dGuo ratio in WBC-DNA but higher concentrations of U-8-oxoGuo compared to controls (p =0.002 and p =0.008, respectively, t-test for independent samples). In the whole group, all urinary biomarkers of nucleic acid oxidation correlated with both the sum of mandelic and phenylglyoxylic acids (rho >0.33, p <0.0001) and 4-vinylphenol (rho >0.29, p <0.001), whereas 8-oxodGuo/105 dGuo in WBC showed a negative correlation with exposure parameters (rho <−0.24, p <0.02). Subjects bearing the hOGG1 Ser/Ser genotype showed lower values of 8-oxodGuo/105 dGuo in WBC than those with at least one variant Cys allele (0.34±0.16 vs 0.45±0.21, p =0.008). In the subgroup of hOGG1 Ser/Ser subjects, laminators showed lower levels of WBC 8-oxodGuo/105 dGuo ratio and significantly higher concentrations of U-8-oxoGua than controls (p =0.07 and p =0.01, respectively, t-test for independent samples). Interestingly, workers showed higher levels of hOGG1 expression compared to controls (p <0.0005). Styrene exposure seems to be associated with oxidation damage to nucleic acids, particularly to RNA and with an induction of the BER system. [Copyright &y& Elsevier]

Abstract: Oxidation of 4-nitro-17β-estradiol (1) with the peroxidase/H2O2 system gave the symmetric C2-linked dimer (3) through phenoxy radical coupling. Similar oxidation of 2-nitro-17β-estradiol (2), in which the nitro group is coplanar with the aromatic ring, yielded 9α- and 9β-hydroxy-2-nitro-17β-estradiol (4a,b), (17β)-2-nitroestra-1(10),2,4,9(11)-tetraene-3,17-diol (5), and (12α,17β)-2-nitroestra-1(10),2,4,9(11)-tetraene-3,12,17-triol (6). With higher concentrations of H2O2, the novel secoestra-1(10),2,4-trien-9-one derivative 7 was obtained from 2. Theoretical calculations suggested that the peculiar behavior of 2 may be due to the generation of a relatively stable radical intermediate at C9, which would then be converted to the reactive quinone methide 8. The chemistry described in this paper appears to be an intriguing example of control of the site of substitution over evolution of phenoxy radicals, and opens new vistas toward selective oxyfunctionalization of the estrane skeleton. [Copyright &y& Elsevier]

Abstract: Oxidation of 5×10-3M noradrenaline in aqueous phosphate buffer, pH 7.4, with K3Fe(CN)6, NaIO4 or Fe2+/EDTA/H2O2 followed by extraction with ethyl acetate and acetylation with Ac2O/Pyr led to a main reaction product which was isolated and identified as 4-[bis-(1H-5,6-diacetoxyindol-2-yl)methyl]-1,2-diacetoxybenzene, an unprecedented [bis-(indol-2-yl)methyl]-benzene derivative unsubstituted on the 3-position of the indole rings. This product was also obtained in 40% yield by reaction of 5,6-dihydroxyindole with 3,4-dihydroxybenzaldehyde. Other components of the oxidation mixture were 1-acetyl-3,5,6-triacetoxyindole, derived from noradrenolutin, and 5,6-diacetoxyindole, originating from cyclisation/dehydration of the o-quinone of noradrenaline, along with some 3,4-diacetoxybenzaldehyde. Inspection of the aqueous phase revealed the presence of 3,4-dihydroxymandelic acid and 3,4-dihydroxybenzaldehyde, derived from oxidative breakdown of the 2-amino-1-hydroxyethyl chain via a p-quinomethane intermediate. These results disclose new aspects of the oxidative chemistry of noradrenaline beyond the aminochrome stage and provide a route to novel [bis-(indol-2-yl)methyl]-benzene derivatives of potential pharmacological interest. [Copyright &y& Elsevier]

In the presence of excess H2O2, oxidation of dopamine was diverted from the usual pigment-forming pathway to afford 6-hydroxydopamine and then a colorless reaction mixture comprising a polar non-extractable product. The latter was obtained in 20% yield by oxidation of 6-hydroxydopamine and was tentatively formulated as the novel 5-(2-aminoethyl)-2-hydroxy-5-(3-hydroxy-2-oxotetrahydro-1aH-oxireno[2,3]cyclopenta[1,2-b]pyrrol-3a(4H)-yl)cyclohex-2-ene-1,4-dione by extensive spectral analysis and conversion to a tetraacetyl derivative. Mechanistic experiments suggested that formation of the product proceeds via 6-hydroxydopamine by H2O2-dependent epoxidation and cyclization steps followed by dimerization and ring contraction with decarboxylation. [Copyright &y& Elsevier]