Established cell lines for safety assessment of food contaminants: differing furazolidone toxicity to V 79, HEp-2 and Caco-2 cells.
In vitro models, preferentially derived from human tissues, may be valuable tools to study the biotransformation and toxicity of compounds that may be present as residues in food products. Such residues may represent a risk to human health, and therefore call for increased testing. Three established cell lines were used to study the toxic effect of furazolidone (FZ), a widely used veterinary drug: HEp-2 cells, derived from a human larynx carcinoma, previously used in toxicity screening of several compounds; Caco-2 cells, derived from a human colon adenocarcinoma, able to differentiate partially in culture, and V 79, a fibroblast cell line derived from Chinese hamster lung, widely used to assess direct toxicants. Various toxicity parameters were used, primarily dealing with cell death and cell proliferation. In all cell lines FZ at a concentration of 5 micrograms/ml caused a marked decrease in cell viability and especially in cell proliferation. Inhibition of DNA synthesis has also been observed, even if at higher concentrations. However, only in V 79 cells was the decrease in cell number accompanied by a marked increase in lactate dehydrogenase leakage due to membrane damage. Moreover, the surviving V 79 cells, after removal of FZ, fully recovered from the effect of the drug, as shown by their full capacity to attach to dishes and to form colonies. Surviving cells of the other two cell lines showed much poorer colony-forming ability. Exposure of Caco-2 cells and, to a lesser extent, HEp-2 cells, caused a marked increase in oxygen consumption, that possibly was due to redox cycling of the initially formed radical nitro anion. Biotransformation of the drug by all three cell lines was accompanied by the formation of protein-bound metabolites, HEp-2 being the most active cells. The toxic effects recorded show that cell lines provide a sensitive system in toxicity assessment. Moreover, it may be suggested that a battery of cell lines, including some of human origin, as well as a battery of endpoints, may be of help in addressing further specific mechanistic investigations.
De Angelis
I
I
Istituto Superiore di Sanità, Laboratorio di Tossicologia Comparata ed Ecotossicologia, Roma, Italy.
Hoogenboom
L A
LA
Huveneers-Oorsprong
M B
MB
Zucco
F
F
Stammati
A
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D003412:Cricetulus; D004350:Drug Residues / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects; D005664:Furazolidone / Q000633:toxicity*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D012680:Sensitivity and Specificity; D013936:Thymidine; D014116:Toxicology / Q000379:methods*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005664:Furazolidone; D007770:L-Lactate Dehydrogenase; D013936:Thymidine