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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Glutathione S-conjugate formation and metabolism in HepG2 cells: a cell model of mercapturic acid biosynthesis.

Authors: Rebbeor, J F; Wang, W; Clifton, D; Ballatori, N

Published In J Toxicol Environ Health A, (1998 Apr 24)

Abstract: Mercapturic acid biosynthesis is mediated by a series of at least four enzymatic steps and three cell membrane transport events, and is believed to require the interorgan shuttling of the various metabolic intermediates. To identify a single cell type that can carry out all of these metabolic and transport steps, the present study examined whether HepG2 cells, a human hepatoma-derived cell line, can convert an electrophilic chemical (1-chloro-2,4-dinitrobenzene, CDNB) to its corresponding mercapturic acid (S-dinitrophenyl-N-acetylcysteine, DNP-NAC). The results demonstrate that HepG2 cells are able to convert CDNB to DNP-NAC in a dose- and time-dependent fashion. Intracellular conjugation with glutathione occurred rapidly, and the resulting glutathione S-conjugate was promptly transported into the culture medium, where it was sequentially degraded to the cysteinylglycine and cysteine S-conjugates. The cysteine conjugate was then presumably reabsorbed, and N-acetylated intracellularly to form the mercapturic acid. The mercapturic acid was found to accumulate slowly in the culture medium, such that after 4 h of incubation, 4-10% of the CDNB dose was recovered as the mercapturic acid. These data provide the first demonstration that a single cell type can carry out all of the transport and enzymatic steps required for mercapturic acid biosynthesis. HepG2 cells may provide a useful model system for studying this important detoxification pathway.

PubMed ID: 9572162 Exiting the NIEHS site

MeSH Terms: Acetylcysteine/analogs & derivatives; Acetylcysteine/metabolism; Acetylcysteine/pharmacokinetics*; Biological Transport; Carcinoma, Hepatocellular; Cysteine/chemistry; Dinitrochlorobenzene/metabolism; Glutathione/metabolism*; Humans; Liver Neoplasms; Metabolic Detoxication, Drug; Models, Biological; Research Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured

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