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The food preservatives, sulphur dioxide and its salts, are known to present some toxic, mutagenic and antinutritional effects; in fact they interact with a number of nutrients, e.g. some vitamins, notably thiamine (Th) and folic acid (FA). The effect of different concentrations of sodium bisulphite in cell culture media has been studied in vitro on a human cell line, HEp-2, deriving from a carcinoma of the larynx. Moreover, the sulphites have been tested with different levels of Th and FA with the aim of elucidating how much the cellular response depended on either the anti-nutritional effect or the toxicity of sulphites. Cell growth has been taken as an index of cytotoxicity and measured both as total protein content and as colony-forming ability. With no Th and FA in the culture medium, a clear decrease of cell growth was observed either with or without addition of sodium bisulphite. A dose-dependent reduction of protein content was detected in cells treated with 10, 50, 100, 200, 250 or 500 microM sodium bisulphite. Moreover, when the cells were treated with 10 or 100 microM of this compound, the colony-forming ability was reduced both in number and colony size. As far as the interaction of the two vitamins with sodium bisulphite is concerned, when these nutrients were present in the medium at 0.5, 1.0, 1.5, 2.0 or 2.5 mg/l, a similar growth profile, determined from their concentration, was observed in treated and control cells, the growth levels being affected by the sodium bisulphite contents. At higher levels of Th and FA, the growth index was still increasing only in treated cells, this phenomenon being particularly evident in cultures treated with 200 microM sodium bisulphite. The colony-forming ability was reduced in controls but still increased in treated cells at the highest concentration of vitamins.

1. The metabolism and cytotoxicity of the antimicrobial nitrofuran drug furazolidone have been studied in Caco-2, HEp-2 and V79 cell lines. Free radical production, metabolite pattern, formation of bound residues, inhibition of cellular replication and protection by the antioxidant glutathione were compared for the three cell lines. 2. All three cell lines produced the same nitro-anion radical with similar kinetics. Little further metabolic breakdown was observed in V79 cells, whereas Caco-2 and HEp-2 cells showed extensive degradation of furazolidone, but with different end patterns. 3. Under hypoxic conditions, the colony-forming ability was extensively impaired in HEp-2 cells whereas the other two cell lines were less affected, suggesting that irreversible damage to DNA occurred prevalently in HEp-2 cells. In V79 cells the absence of oxygen caused a 25-fold increase in the formation of protein-bound residues. 4. Brief exposure to furazolidone caused a 50% loss of endogenous glutathione in Caco-2 cells, but no loss could be detected in V79 and HEp-2 cells. Consistently, when glutathione was depleted by buthionine-[S,R]-sulphoximine (BSO) and diethylmaleate (DEM) treatment, the viability of V79 and HEp-2 cells was minimally affected by furazolidone, whereas that of Caco-2 cells was substantially reduced. 5. It is concluded that the cytotoxicity of furazolidone in these cell lines can be exerted by a number of different mechanisms, possibly related to different metabolic pathways. The cytotoxicity of nitrofuran drugs, therefore, cannot be ascribed to a single toxic intermediate, but in Caco-2 cells furazolidone is extensively metabolized and detoxified by GSH, in V79 is only partially activated and then bound to proteins, whereas in HEp-2, once activated, may react with DNA.