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Open Access

Impact of stereochemistry on biological effects of permethrin: induction of apoptosis in human hepatoma cells (HCC-1.2) and primary rat hepatocyte cultures

  • Julia Dornetshuber1,
  • Wolfgang Bicker2,
  • Michael Lämmerhofer2,
  • Wolfgang Lindner2,
  • Anneliese Karwan1 and
  • Wilfried Bursch1Email author
BMC Pharmacology20077(Suppl 2):A65

Published: 14 November 2007

Stereochemistry plays a crucial role in determining the toxicological profile of many chiral xenobiotics, e.g. the insecticidal action of mixtures containing the four stereoisomers of permethrin is essentially brought about by the (1R, cis)- and (1R, trans)-forms. Primarily non-ion channel related mammalian effects like induction of cytochrome P450 enzymes and inhibition of mitochondrial complex I – relevant endpoints in elucidating a chemical's mode of action and thus toxicological risk assessment – were elucidated in studies with four-isomer mixtures of permethrin only [13]. Therefore, we initiated a project to shed light on the stereoselectivity of permethrin effects in mammals, using human hepatoma cells (HCC-1.2) and primary rat hepatocyte cultures as test models. Here we report (1) a commercially available four-isomer mixture of permethrin (cis-racemate/trans-racemate ~ 25:75) exhibited a dose-dependent (2–50 μM) pro-apoptotic activity; (2) the physiological death signal TGF-β1 (10 ng/ml) and permethrin exerted an additive pro-apoptotic effect; (3) purified permethrin stereoisomers, i.e. (1R, cis), (1S, cis), (1R, trans), (1S, trans), exhibited – in contrast to their insecticidal action – no significant differences in their pro-apoptotic action as compared to the four-isomer mixture; (4) the pro-apoptotic potency of permethrin was lost upon metabolism to permethrinic acid, 3-phenoxybenzyl alcohol, and 3-phenoxybenzoic acid.

Authors’ Affiliations

Department of Medicine I, Institute of Cancer Research, Research Unit Toxicology and Prevention, Medical University of Vienna
Institute of Analytical Chemistry and Food Chemistry, University of Vienna


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© Dornetshuber et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.