Analysis of structure-cytotoxicity in vitro relationship (SAR) for perfluorinated carboxylic acids.
Perfluorinated carboxylic acids (PFAs) represent derivatives of naturally occurring compounds and have been widely used in various industrial fields for decades. They are known to be environmentally persistent. Thus far numerous reports have been focused on reproductive toxicity of PFAs in animals but few studies have been carried out on toxicity towards human cells. Viability tests were performed here at varying time-exposures on C6-C18 PFAs with human colon carcinoma (HCT116) cells. These cells were found earlier as the most useful line for in vitro assays. A chain length-EC50 dependence has been clearly observed. Estimated values of EC50 decreased with elongation of fluorocarbon chain (PFHxA > PFHpA > PFOA > PFNA > PFDA > PFDoA > PFTeDA). Further elongation (C16 and C18) did not deepen the effect but even partially reversed it. The effect was intensified after longer exposure (72 h); at relatively low 40 microM PFTeDA, the viability decreased to approximately 50%. It seems that PFAs are not acutely toxic at the cellular level. Even so, however, they can trigger cell apoptosis, which is prominent in the case of myristic acid perfluorinated analogue.
Kleszczyński
Konrad
K
Intercollegiate Faculty of Biotechnology, Department of Molecular Enzymology, Medical University of Gdańsk, ul. Debinki 1, 80-211 Gdańsk, Poland.
Gardzielewski
Paweł
P
Mulkiewicz
Ewa
E
Stepnowski
Piotr
P
Składanowski
Andrzej C
AC
D002264:Carboxylic Acids / Q000737:chemistry / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity; D005466:Fluorocarbons / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons