Use of a flow cell bioreactor as a chronic toxicity model system

We describe the use of a model system to mimic chronic toxin exposure, simi lar to that which might be found in a human situation, where exposure to di etary or environmental toxins occurs at a low level for an extended period of time. This is in contrast to the acute, immediately toxic dose effect us ually observed in Bask tissue culture. The apparatus used was a flow cell b ioreactor in which cells can be cultured for lengthy periods of time as a c ontinuous viable population. The compound used as the toxic agent was 3-nit ropropanoic acid (3-NPA), a fungal neurotoxin which acts as a suicide inhib itor of succinate dehydrogenase. The secondary human cell line, Int 407, wa s tested in conventional flask culture for periods of up to 72 hours to det ermine the no-observed-effect level (NOEL) for 3-NPA. Cell populations esta blished in the bioreactor were continuously er;posed to levels of 3-NPA bel ow that of the NOEL for periods of up to 4 weeks and the viability of the p opulation determined using MTT, trypan blue and ATP assays. (C) 1999 Elsevi er Science Ltd. All rights reserved.