Cytotoxicity in vitro of organotin compounds to fish hepatoma cells PLHC-1 ( Poeciliopsis lucida)

Abstract

Cytotoxicity in vitro to fish hepatoma cells PLHC-1 has been analyzed for a series of 21 organotin compounds consisting of all degrees of alkylation and arylation. The sensitivity of the neutral red (NR) assay and the tetrazolium salt reduction (MTT) assay was similar for most of the organotin compounds. Cytotoxic effects were found at concentrations between 10 −8 M and 10 −2 M. For various trisubstituted organotin compounds, including tributyltin and triphenyltin, which are used in antifouling paints and as pesticides, respectively, cytotoxic concentrations in the range of 10 −8 M to 10 −6 M were observed. Based on the concentration reducing NR uptake by 50% (NR 50), the sequence of Cytotoxicity amongst butyltins was tributyltin ⪢ bis(tributyl)-tin ⪢ dibutyltin ⪢ tetrabutyltin ⪢ butyltin ⪢ tin(IV). Tributyltin induced effects on cell functions quickly, as a reduction in NR uptake by 30% was recorded after 30 min exposure to 4 · 10 −7 M. The ranking order in Cytotoxicity in the MTT assay of phenylated organotins was triphenyltin ⪢ diphenyltin ⪢ phenyltin ⪢ tin(IV). Cytotoxic concentrations of tributyltin and triphenyltin measured in the bromodeoxyuridine (BrdU) assay and with the crystal violet (CV) staining method do not differ significantly from those determined in the NR and MTT assay. Tri-and disubstituted organotin compounds exhibit a significant correlation between the noctanol/water partition coefficient (logK ow) and the NR 50 ( n = 10, r = 0.86, P = 0.001) and the MTT 50 values ( n = 11, r = 0.85, P = 0.001), respectively. In addition, good qualitative correlations between in vitro Cytotoxicity data and in vivo fish toxicity data were found (for NR assay n = 8, r = 0.86, P = 0.001; for MTT assay n = 9, r = 0.80, P = 0.001). he results indicate that the in vitro Cytotoxicity assays using PLHC-1 cells are useful tools for the estimation of the acute toxicity to fish of organotins and possibly other compounds.