Aflatoxin B1 metabolism and DNA binding in isolated hepatocytes from rainbow trout (Salmo gairdneri)

Abstract

The World Health Organisation (WHO) has recently recommended the use of a simple in vitro test (Nitrosation Assay Procedure, NAP) to allow the ranking of orally administered drugs. It was suggested that the ranking of drugs should be carried out on a reactivity scale, according to their ability to nitrosate in the presence of high concentrations of nitrite at low pH (3–4). The present study was undertaken to investigate the effect of adding the concentration of nitrite recommended for the NAP Test (40 mM) to normal fasting human gastric juice. The data dearly demonstrate that such treatment results in the formation of derivatives with specific mutagenic activity for the bacterium Salmonella typhi-murium TA1537. This strain was recommended for use in the NAP Test. Although the NAP Test may be valid for its original purpose, in the absence of more physiologically relevant data it is invalid for use as a final arbiter in risk-benefit assessments. The possible formation of mutagenic species as a result of the nitrosation of natural gastric secretions should be considered when any risk-benefit assessment is made.