Detail of "26289-39-4"

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Mutagenicity of halogenated and other substituted dinitrobenzenes in Salmonella typhimurium TA100 and derivatives deficient in glutathione (TA100/GSH-) and nitroreductase (TA100NR)

Mutagenicity of halogenated and other substituted dinitrobenzenes in Salmonella typhimurium TA100 and derivatives deficient in glutathione (TA100/GSH-) and nitroreductase (TA100NR). Kerklaan, P. R. M.; Bouter, S.; Te Koppele, J. M.; Vermeulen, N. P. E.; Van Bladeren, P. J.; Mohn, G. R. (Dep. Radiat. Genet. Chem. Mutagen., State Univ. Leiden, Leiden 2333, Neth.). Mutat. Res., 176(2), 171-8 (English) 1987. CODEN: MUREAV. 584-48-5 and 23815-63-6 are cas registry numbers of chemicals which are used as reagents here. ISSN: 0027-5107. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) A series of mutagenicity tests were performed to det. how 1-chloro-2,4-dinitrobenzene (CDNB)(I) [97-00-7] could be activated after reaction with GSH [70-18-8] . In liq. preincubation assays, strains TA100, TA100/GSH-, and TA100NR, a nitroreductase-deficient deriv. of TA100, were treated with CDNB and its fluoro and bromo analog (FDNB [70-34-8] and BDNB [584-48-5]), further with its GSH conjugate (S-GSH-DNB [26289-39-4]) and possible metabolic products, such as S-cysteine - dinitrobenzene (S-Cys-DNB) [23815-63-6] and S-methyl-dinitrobenzene (S-Me DNB) [2363-23-7], and with 2 more analoges, O-methyl-dinitrobenzene (O-methyl-DNB) [119-27-7] and dinitrobenzene (DNB) [99-65-0]. CDNB, FDNB, and BDNB were mutagenic in TA100 and TA100NR, while TA100/GSH- was much less sensitive to the mutagenic action of these halogenated dinitrobenzenes. DNB, O-methyl-DNB, S-methyl-DNB, and S-Cys-DNB induced equal nos. of His+ revertants in TA100 and TA100/GSH-, but were not mutagenic in TA100NR. S-GSH-DNB showed no mutagenic activity in any of the 3 strains under the present exptl. conditions. Apparently, the halogenated aroms. may react with bacterial DNA and produce premutagenic alterations according to 2 mechanisms: (1) direct attack on the DNA through nucleophilic substitution (Sn2) of the halogen atoms; (2) activation through GSH conjugation and subsequent nitroredn. of the conjugate or its metabolic products to more reactive intermediates. .

Excretion of glutathione conjugates by primary cultured rat hepatocytes

Excretion of glutathione conjugates by primary cultured rat hepatocytes. Lindwall, Glen; Boyer, Thomas D. (V. A. Med. Cent., Univ. California, San Francisco, CA 94121, USA). J. Biol. Chem., 262(11), 5151-8 (English) 1987. CODEN: JBCHA3. ISSN: 0021-9258. DOCUMENT TYPE: Journal CA Section: 13 (Mammalian Biochemistry) Since conjugation of xenobiotics with GSH occurs commonly within the liver and these GSH conjugates are then preferentially excreted into bile, this excretory process was characterized by using primary cultured hepatocytes (24 h). 1-Chloro-2,4-dinitrobenzene rapidly entered the cells and formed a GSH conjugate, S-(dinitrophenyl)glutathione (GS-DNP), irresp. of the temp. of incubation. In contrast, the efflux of the GSH conjugate was essentially absent in the cold but recovered rapidly upon rewarming of the cells. Therefore, initial rates of efflux of the conjugate at 37° were measured from cells preloaded biosynthetically at 10°. Efflux was a saturable process with respect to intracellular GS-DNP with an apparent Km of 0.58 mM and Vmax of 0.15 nmol/min/mg protein. The excretion of GS-DNP had an energy of activation of 15. 26289-39-4 and 97-00-7 which are cas registry numbers of chemicals are mentioned.3 kcal/mol. The GSH conjugate of p-nitrobenzylchloride when formed within the hepatocytes acted as a competitive inhibitor of GS-DNP efflux. Cultured hepatocytes, therefore, appeared to have a specific transport process for the excretion of GSH conjugates. The addn. of GS-DNP, but not GSH, GSSG, or methionine, to the medium caused a decrease in the rate of efflux of radiolabeled GS-DNP. The hepatocytes were able, however, to excrete the GSH conjugate against an excess of extracellular GS-DNP. Apparently, extracellular GS-DNP, although capable of binding to the carrier, entered the hepatocytes quite slowly relative to rates of efflux. This carrier may function in a manner that would minimize the reuptake by hepatocytes of conjugates that have been excreted into the bile. .