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Vamvakas S, Dekant W, Henschler D. Genotoxicity of haloalkene and haloalkane glutathione S-conjugates in porcine kidney cells. Toxicol In Vitro. 1989;3(2):151-6doi: 10.1016/0887-2333(89)90058-1.
Vamvakas, S., Dekant, W., & Henschler, D. (1989). Genotoxicity of haloalkene and haloalkane glutathione S-conjugates in porcine kidney cells. Toxicology in vitro : an international journal published in association with BIBRA, 3(2), 151-6. https://doi.org/10.1016/0887-2333(89)90058-1
Vamvakas, S, et al. "Genotoxicity of haloalkene and haloalkane glutathione S-conjugates in porcine kidney cells." Toxicology in vitro : an international journal published in association with BIBRA vol. 3,2 (1989): 151-6. doi: https://doi.org/10.1016/0887-2333(89)90058-1
Vamvakas S, Dekant W, Henschler D. Genotoxicity of haloalkene and haloalkane glutathione S-conjugates in porcine kidney cells. Toxicol In Vitro. 1989;3(2):151-6. doi: 10.1016/0887-2333(89)90058-1. PMID: 20702313.
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Toxicol In Vitro. 1989;3(2):151-6. doi: 10.1016/0887-2333(89)90058-1.

Genotoxicity of haloalkene and haloalkane glutathione S-conjugates in porcine kidney cells.

Toxicology in vitro : an international journal published in association with BIBRA

S Vamvakas, W Dekant, D Henschler

Affiliations

  1. Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, D-8700 Würzburg, FRG.

PMID: 20702313 DOI: 10.1016/0887-2333(89)90058-1

Abstract

The genotoxicity of the glutathione S-conjugates S-(12-dichlorovinyl)glutathione (DCVG), S-(1,2,2-trichlorovinyl)glutathione (TCVG), S-(1,2,3,4,4-pentachlorobutadienyl)glutathione (PCBG) and S-(2-chloroethyl)glutathione (CEG) was investigated in LLC-PK1, a cultured line of porcine kidney cells that exhibits many properties of proximal tubular cells. DNA damage caused by treatment of the cells with the S-conjugates was estimated by determining the induction of unscheduled DNA synthesis (UDS) after inhibition of replicative DNA synthesis in confluent LLC-PK1 monolayers. DCVG-, TCVG- and PCBG-induced dose-dependent UDS at concentrations not causing cytotoxicity, as determined by the release of lactate dehydrogenase into the medium. Acivicin, which inhibits irreversibly gamma-glutamyl-transpeptidase (GGT) and aminooxyacetic acid, an inhibitor of cysteine conjugate beta-lyase, blocked DCVG-, TCVG- and PCBG-induced genotoxicity. CEG, however, was genotoxic in subconfluent cells and this was not dependent on GGT and beta-lyase activities. The DNA damaging effects in kidney cells of DCVG, TCVG and PCBG, which are metabolites of the nephrocarcinogens trichloroethylene, tetrachloroethylene and hexachlorobutadiene, respectively, suggest that the parent haloalkenes are potentially genotoxic in the rat kidney, the target organ for both acute toxicity and carcinogenicity.

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