title: The cyto- and genotoxicity of organotin compounds is dependent on the cellular uptake capability.
abstract: Organotin compounds have been widely used as stabilizers and anti-fouling agents with the result that they are ubiquitously distributed in the environment. Organotins accumulate in the food chain and potential effects on human health are disquieting. It is not known as yet whether cell surface adsorption or accumulation within the cell, or indeed both is a prerequisite for the toxicity of organotin compounds. In this study, the alkylated tin derivatives monomethyltin trichloride (MMT), dimethyltin dichloride (DMT), trimethyltin chloride (TMT) and tetramethyltin (TetraMT) were investigated for cyto- and genotoxic effects in CHO-9 cells in relation to the cellular uptake. To identify genotoxic effects, induction of micronuclei (MN), chromosome aberrations (CA) and sister chromatid exchanges (SCE) were analyzed and the nuclear division index (NDI) was calculated. The cellular uptake was assessed using ICP-MS analysis. The toxicity of the tin compounds was also evaluated after forced uptake by electroporation. Our results show that uptake of the organotin compounds was generally low but dose-dependent. Only weak genotoxic effects were observed after exposure of cells to DMT and TMT. MMT and TetraMT were negative in the test systems. After forced uptake by electroporation MMT, DMT and TMT induced significant DNA damage at non-cytotoxic concentrations. The results presented here indicate a considerable toxicological potential of some organotin species but demonstrate clearly that the toxicity is modulated by the cellular uptake capability.
authors.affiliation: Institute of Hygiene and Occupational Medicine, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany. elke.dopp@uni-essen.de
authors.forename: E
authors.initials: E
authors.lastname: Dopp
authors.forename: L M
authors.initials: LM
authors.lastname: Hartmann
authors.forename: U
authors.initials: U
authors.lastname: von Recklinghausen
authors.forename: A M
authors.initials: AM
authors.lastname: Florea
authors.forename: S
authors.initials: S
authors.lastname: Rabieh
authors.forename: B
authors.initials: B
authors.lastname: Shokouhi
authors.forename: A V
authors.initials: AV
authors.lastname: Hirner
authors.forename: G
authors.initials: G
authors.lastname: Obe
authors.forename: A W
authors.initials: AW
authors.lastname: Rettenmeier
mesh_terms: D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced*; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D018274:Electroporation; D013058:Mass Spectrometry; D015162:Micronucleus Tests; D009947:Organotin Compounds / Q000493:pharmacokinetics* / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects*
chemical_list: D009947:Organotin Compounds