Assessment of unscheduled DNA synthesis in a cultured line of renal epithelial cells exposed to cysteine S-conjugates of haloalkenes and haloalkanes.
The ability of S-(1,2-dichlorovinyl)-L-cysteine (DCVC), S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC), S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine (PCBC), S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFEC) and S-(2-chloroethyl)-L-cysteine (CEC) to induce DNA repair was investigated in LLC-PK1, a cultured line of porcine kidney tubular epithelial cells. DNA repair due to exposure of the cells to the S-conjugates was determined as unscheduled DNA synthesis (UDS) after inhibition of replicative DNA synthesis in confluent LLC-PK1 monolayers. DCVC, TCVC and PCBC induced dose-dependent UDS in LLC-PK1 at concentrations which did not impair the viability of the cells compared to untreated controls; higher concentrations were cytotoxic, resulting in lactate dehydrogenase leakage into the medium. Cell death was also induced by CTFEC, which failed to exert genotoxicity. CEC induced the highest response among these cysteine conjugates without impairing cell viability. Inhibition of cysteine conjugate beta-lyase with aminooxyacetic acid abolished the effects of DCVC, TCVC, PCBC and CTFEC but did not influence the genotoxicity of CEC.
Vamvakas
S
S
Institut für Toxikologie, Universität Würzburg, F.R.G.
Dekant
W
W
Henschler
D
D
D000818:Animals; D013437:Carbon-Sulfur Lyases; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D006846:Hydrocarbons, Halogenated; D066298:In Vitro Techniques; D007668:Kidney; D008190:Lyases / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine
D006846:Hydrocarbons, Halogenated; D008190:Lyases; D013437:Carbon-Sulfur Lyases; C019969:S-alkylcysteine lyase; D003545:Cysteine