The role of nitric oxide on DNA damage induced by benzene metabolites

Abstract

Benzene, a tobacco constituent, is a leukemogen in humans and a carcinogen in rodents. Several benzene metabolites generate superoxide anion (O 2 •− ) and induce nitric oxide synthase in the bone marrow of mice. We hypothesized that the reaction of nitric oxide ( • NO) with O 2•− leads to the formation of peroxynitrite as an intermediate during benzene metabolism. This hypothesis was supported by demonstrating that the exposure of mice to benzene produced nitrated metabolites and enhanced the levels of protein-bound 3-nitrotyrosine in the bone marrow of mice in vivo. In the current study, we investigated the influence of nitric oxide, generated from sodium 1-(N,Ndiethylamino)diazen-1-ium-1,2-diolate, on DNA strand breaks induced by each single or binary benzene metabolite at different doses and compared the levels of the DNA damage induced by each benzene metabolite in the presence of nitric oxide with the levels of DNA strand breaks induced by peroxynitrite at similar doses in vitro. We found that among benzene metabolites only 1,2,4-trihydroxybenzene (BT) can induce significant DNA damage in the absence of nitric oxide.

Pengaruh suplementasi vitamin e (α-tokoferol) terhadap kadar gamma glutamil transferase (ggt) dan kadar nitric oxide (no) pada tikus (Studi pada tikus rattus novergicus strain wistar jantan terpapar inhalasi uap benzene)

“…(33) Adanya radikal bebas akan menginduksi iNOS di makrofag untuk menghasilkan NO dan ROS. (34) iNOS terlibat dalam konversi Larginin menjadi •NO dan citrulline. iNOS adalah sitokrom P-450 jenis hemoprotein yang mengandug domain reduktase dan heme pada polipeptida yang sama.…”

“…iNOS adalah sitokrom P-450 jenis hemoprotein yang mengandug domain reduktase dan heme pada polipeptida yang sama. (11), (34) Peningkatan kadar NO merupakan mekanisme pertahanan tubuh sebagai sitotoksik terhadap senyawa toksik (benzene dan metabolitnya) dan bagian dari upaya sel dalam menjaga homeostasis terhadap stres oksidatif. (35) Namun, rangsangan produksi NO dan superoksida oleh iNOS dapat menyebabkan pembentukan peroksinitrit (ONOO -), suatu perantara reaktif yang diketahui menyebabkan kerusakan protein melalui nitrasi tirosin, triptofan atau residu sistein.…”

The role of catechols and free radicals in benzene toxicity: An oxidative DNA damage pathway

“…The simplest catechol (1,2-dihydroxybenzene) is an aromatic hydrocarbon metabolite of benzene that has cytotoxic, haematotoxic, immunotoxic, and genotoxic properties [She et al, 2006;Kondrová et al, 2007;Melikian et al, 2008;Shen et al, 2008], and is extensively used in industry as a volatile solvent or material for the synthe-sis of other chemicals [Andrews and Snyder, 1991]. Currently, concern is focused on the effects of long-term occupational and environmental exposure to low levels of benzene [Zhu et al, 2001].…”

Enhanced photocatalytic degradation of a phenolic compounds’ mixture using a highly efficient TiO2/reduced graphene oxide nanocomposite

“…Comparing the degradation rate constants for phenol and CP in the mixture, it can be noticed that they were very similar (except in case of rGOTi in the presence of H 2 O 2 using UV or Xe) because of the aforementioned reason. Secondly, the degradation rate constants of any phenolic compound (alone or in a mixture; see Tables 3,4) in the presence of H 2 O 2 are significantly higher than those in its absence regardless of the type [66,67]. Therefore, this peak overlapped with the peak of the remaining phenol and showed higher absorbance of phenol, i.e., false lower conversion rate which is not the real case.…”